From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation

From Sponge to Scaffold: Re-centering lncRNAs in... | F1000Research "use strict";function _typeof(t){return(_typeof="function"==typeof Symbol&&"symbol"==typeof Symbol.iterator?function(t){return typeof t}:function(t){return t&&"function"==typeof Symbol&&t.constructor===Symbol&&t!==Symbol.prototype?"symbol":typeof t})(t)}!function(){var t=function(){var t,e,o=[],n=window,r=n;for(;r;){try{if(r.frames.__tcfapiLocator){t=r;break}}catch(t){}if(r===n.top)break;r=r.parent}t||(!function t(){var e=n.document,o=!!n.frames.__tcfapiLocator;if(!o)if(e.body){var r=e.createElement("iframe");r.style.cssText="display:none",r.name="__tcfapiLocator",e.body.appendChild(r)}else setTimeout(t,5);return!o}(),n.__tcfapi=function(){for(var t=arguments.length,n=new Array(t),r=0;r 3&&2===parseInt(n[1],10)&&"boolean"==typeof n[3]&&(e=n[3],"function"==typeof n[2]&&n[2]("set",!0)):"ping"===n[0]?"function"==typeof n[2]&&n[2]({gdprApplies:e,cmpLoaded:!1,cmpStatus:"stub"}):o.push(n)},n.addEventListener("message",(function(t){var e="string"==typeof t.data,o={};if(e)try{o=JSON.parse(t.data)}catch(t){}else o=t.data;var n="object"===_typeof(o)&&null!==o?o.__tcfapiCall:null;n&&window.__tcfapi(n.command,n.version,(function(o,r){var a={__tcfapiReturn:{returnValue:o,success:r,callId:n.callId}};t&&t.source&&t.source.postMessage&&t.source.postMessage(e?JSON.stringify(a):a,"*")}),n.parameter)}),!1))};"undefined"!=typeof module?module.exports=t:t()}(); dataLayer = dataLayer || []; // Standard GTM initialization - Google Consent Mode handles consent automatically (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl+ '>m_auth=hzk0Vc3qFsQYhCrIoHz68A>m_preview=env-1>m_cookies_win=x';f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-MWFK8L5J'); ;window.NREUM||(NREUM={});NREUM.init={distributed_tracing:{enabled:true},privacy:{cookies_enabled:true},ajax:{deny_list:["bam.nr-data.net"]}}; ;NREUM.loader_config={accountID:"438030",trustKey:"438030",agentID:"772317073",licenseKey:"97f8f67f26",applicationID:"772317073"} ;NREUM.info={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net",licenseKey:"97f8f67f26",applicationID:"772317073",sa:1} ;/*! For license information please see nr-loader-spa-1.236.0.min.js.LICENSE.txt */ (()=>{"use strict";var e,t,r={5763:(e,t,r)=>{r.d(t,{P_:()=>l,Mt:()=>g,C5:()=>s,DL:()=>v,OP:()=>T,lF:()=>D,Yu:()=>y,Dg:()=>h,CX:()=>c,GE:()=>b,sU:()=>_});var n=r(8632),i=r(9567);const o={beacon:n.ce.beacon,errorBeacon:n.ce.errorBeacon,licenseKey:void 0,applicationID:void 0,sa:void 0,queueTime:void 0,applicationTime:void 0,ttGuid:void 0,user:void 0,account:void 0,product:void 0,extra:void 0,jsAttributes:{},userAttributes:void 0,atts:void 0,transactionName:void 0,tNamePlain:void 0},a={};function s(e){if(!e)throw new Error("All info objects require an agent identifier!");if(!a[e])throw new Error("Info for ".concat(e," was never set"));return a[e]}function c(e,t){if(!e)throw new Error("All info objects require an agent identifier!");a[e]=(0,i.D)(t,o),(0,n.Qy)(e,a[e],"info")}var u=r(7056);const d=()=>{const e={blockSelector:"[data-nr-block]",maskInputOptions:{password:!0}};return{allow_bfcache:!0,privacy:{cookies_enabled:!0},ajax:{deny_list:void 0,enabled:!0,harvestTimeSeconds:10},distributed_tracing:{enabled:void 0,exclude_newrelic_header:void 0,cors_use_newrelic_header:void 0,cors_use_tracecontext_headers:void 0,allowed_origins:void 0},session:{domain:void 0,expiresMs:u.oD,inactiveMs:u.Hb},ssl:void 0,obfuscate:void 0,jserrors:{enabled:!0,harvestTimeSeconds:10},metrics:{enabled:!0},page_action:{enabled:!0,harvestTimeSeconds:30},page_view_event:{enabled:!0},page_view_timing:{enabled:!0,harvestTimeSeconds:30,long_task:!1},session_trace:{enabled:!0,harvestTimeSeconds:10},harvest:{tooManyRequestsDelay:60},session_replay:{enabled:!1,harvestTimeSeconds:60,sampleRate:.1,errorSampleRate:.1,maskTextSelector:"*",maskAllInputs:!0,get blockClass(){return"nr-block"},get ignoreClass(){return"nr-ignore"},get maskTextClass(){return"nr-mask"},get blockSelector(){return e.blockSelector},set blockSelector(t){e.blockSelector+=",".concat(t)},get maskInputOptions(){return e.maskInputOptions},set maskInputOptions(t){e.maskInputOptions={...t,password:!0}}},spa:{enabled:!0,harvestTimeSeconds:10}}},f={};function l(e){if(!e)throw new Error("All configuration objects require an agent identifier!");if(!f[e])throw new Error("Configuration for ".concat(e," was never set"));return f[e]}function h(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");f[e]=(0,i.D)(t,d()),(0,n.Qy)(e,f[e],"config")}function g(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");var r=l(e);if(r){for(var n=t.split("."),i=0;i {r.d(t,{D:()=>i});var n=r(50);function i(e,t){try{if(!e||"object"!=typeof e)return(0,n.Z)("Setting a Configurable requires an object as input");if(!t||"object"!=typeof t)return(0,n.Z)("Setting a Configurable requires a model to set its initial properties");const r=Object.create(Object.getPrototypeOf(t),Object.getOwnPropertyDescriptors(t)),o=0===Object.keys(r).length?e:r;for(let a in o)if(void 0!==e[a])try{"object"==typeof e[a]&&"object"==typeof t[a]?r[a]=i(e[a],t[a]):r[a]=e[a]}catch(e){(0,n.Z)("An error occurred while setting a property of a Configurable",e)}return r}catch(e){(0,n.Z)("An error occured while setting a Configurable",e)}}},6818:(e,t,r)=>{r.d(t,{Re:()=>i,gF:()=>o,q4:()=>n});const n="1.236.0",i="PROD",o="CDN"},385:(e,t,r)=>{r.d(t,{FN:()=>a,IF:()=>u,Nk:()=>f,Tt:()=>s,_A:()=>o,il:()=>n,pL:()=>c,v6:()=>i,w1:()=>d});const n="undefined"!=typeof window&&!!window.document,i="undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self.navigator instanceof WorkerNavigator||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis.navigator instanceof WorkerNavigator),o=n?window:"undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis),a=""+o?.location,s=/iPad|iPhone|iPod/.test(navigator.userAgent),c=s&&"undefined"==typeof SharedWorker,u=(()=>{const e=navigator.userAgent.match(/Firefox[/\s](\d+\.\d+)/);return Array.isArray(e)&&e.length>=2?+e[1]:0})(),d=Boolean(n&&window.document.documentMode),f=!!navigator.sendBeacon},1117:(e,t,r)=>{r.d(t,{w:()=>o});var n=r(50);const i={agentIdentifier:"",ee:void 0};class o{constructor(e){try{if("object"!=typeof e)return(0,n.Z)("shared context requires an object as input");this.sharedContext={},Object.assign(this.sharedContext,i),Object.entries(e).forEach((e=>{let[t,r]=e;Object.keys(i).includes(t)&&(this.sharedContext[t]=r)}))}catch(e){(0,n.Z)("An error occured while setting SharedContext",e)}}}},8e3:(e,t,r)=>{r.d(t,{L:()=>d,R:()=>c});var n=r(2177),i=r(1284),o=r(4322),a=r(3325);const s={};function c(e,t){const r={staged:!1,priority:a.p[t]||0};u(e),s[e].get(t)||s[e].set(t,r)}function u(e){e&&(s[e]||(s[e]=new Map))}function d(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:"",t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:"feature";if(u(e),!e||!s[e].get(t))return a(t);s[e].get(t).staged=!0;const r=[...s[e]];function a(t){const r=e?n.ee.get(e):n.ee,a=o.X.handlers;if(r.backlog&&a){var s=r.backlog[t],c=a[t];if(c){for(var u=0;s&&u {let[t,r]=e;return r.staged}))&&(r.sort(((e,t)=>e[1].priority-t[1].priority)),r.forEach((e=>{let[t]=e;a(t)})))}function f(e,t){var r=e[1];(0,i.D)(t[r],(function(t,r){var n=e[0];if(r[0]===n){var i=r[1],o=e[3],a=e[2];i.apply(o,a)}}))}},2177:(e,t,r)=>{r.d(t,{c:()=>f,ee:()=>u});var n=r(8632),i=r(2210),o=r(1284),a=r(5763),s="nr@context";let c=(0,n.fP)();var u;function d(){}function f(e){return(0,i.X)(e,s,l)}function l(){return new d}function h(){u.aborted=!0,u.backlog={}}c.ee?u=c.ee:(u=function e(t,r){var n={},c={},f={},g=!1;try{g=16===r.length&&(0,a.OP)(r).isolatedBacklog}catch(e){}var p={on:b,addEventListener:b,removeEventListener:y,emit:v,get:x,listeners:w,context:m,buffer:A,abort:h,aborted:!1,isBuffering:E,debugId:r,backlog:g?{}:t&&"object"==typeof t.backlog?t.backlog:{}};return p;function m(e){return e&&e instanceof d?e:e?(0,i.X)(e,s,l):l()}function v(e,r,n,i,o){if(!1!==o&&(o=!0),!u.aborted||i){t&&o&&t.emit(e,r,n);for(var a=m(n),s=w(e),d=s.length,f=0;fn,p:()=>i});var n=r(2177).ee.get("handle");function i(e,t,r,i,o){o?(o.buffer([e],i),o.emit(e,t,r)):(n.buffer([e],i),n.emit(e,t,r))}},4322:(e,t,r)=>{r.d(t,{X:()=>o});var n=r(5546);o.on=a;var i=o.handlers={};function o(e,t,r,o){a(o||n.E,i,e,t,r)}function a(e,t,r,i,o){o||(o="feature"),e||(e=n.E);var a=t[o]=t[o]||{};(a[r]=a[r]||[]).push([e,i])}},3239:(e,t,r)=>{r.d(t,{bP:()=>s,iz:()=>c,m$:()=>a});var n=r(385);let i=!1,o=!1;try{const e={get passive(){return i=!0,!1},get signal(){return o=!0,!1}};n._A.addEventListener("test",null,e),n._A.removeEventListener("test",null,e)}catch(e){}function a(e,t){return i||o?{capture:!!e,passive:i,signal:t}:!!e}function s(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;window.addEventListener(e,t,a(r,n))}function c(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;document.addEventListener(e,t,a(r,n))}},4402:(e,t,r)=>{r.d(t,{Ht:()=>u,M:()=>c,Rl:()=>a,ky:()=>s});var n=r(385);const i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx";function o(e,t){return e?15&e[t]:16*Math.random()|0}function a(){const e=n._A?.crypto||n._A?.msCrypto;let t,r=0;return e&&e.getRandomValues&&(t=e.getRandomValues(new Uint8Array(31))),i.split("").map((e=>"x"===e?o(t,++r).toString(16):"y"===e?(3&o()|8).toString(16):e)).join("")}function s(e){const t=n._A?.crypto||n._A?.msCrypto;let r,i=0;t&&t.getRandomValues&&(r=t.getRandomValues(new Uint8Array(31)));const a=[];for(var s=0;s {r.d(t,{Bq:()=>n,Hb:()=>o,oD:()=>i});const n="NRBA",i=144e5,o=18e5},7894:(e,t,r)=>{function n(){return Math.round(performance.now())}r.d(t,{z:()=>n})},7243:(e,t,r)=>{r.d(t,{e:()=>o});var n=r(385),i={};function o(e){if(e in i)return i[e];if(0===(e||"").indexOf("data:"))return{protocol:"data"};let t;var r=n._A?.location,o={};if(n.il)t=document.createElement("a"),t.href=e;else try{t=new URL(e,r.href)}catch(e){return o}o.port=t.port;var a=t.href.split("://");!o.port&&a[1]&&(o.port=a[1].split("/")[0].split("@").pop().split(":")[1]),o.port&&"0"!==o.port||(o.port="https"===a[0]?"443":"80"),o.hostname=t.hostname||r.hostname,o.pathname=t.pathname,o.protocol=a[0],"/"!==o.pathname.charAt(0)&&(o.pathname="/"+o.pathname);var s=!t.protocol||":"===t.protocol||t.protocol===r.protocol,c=t.hostname===r.hostname&&t.port===r.port;return o.sameOrigin=s&&(!t.hostname||c),"/"===o.pathname&&(i[e]=o),o}},50:(e,t,r)=>{function n(e,t){"function"==typeof console.warn&&(console.warn("New Relic: ".concat(e)),t&&console.warn(t))}r.d(t,{Z:()=>n})},2587:(e,t,r)=>{r.d(t,{N:()=>c,T:()=>u});var n=r(2177),i=r(5546),o=r(8e3),a=r(3325);const s={stn:[a.D.sessionTrace],err:[a.D.jserrors,a.D.metrics],ins:[a.D.pageAction],spa:[a.D.spa],sr:[a.D.sessionReplay,a.D.sessionTrace]};function c(e,t){const r=n.ee.get(t);e&&"object"==typeof e&&(Object.entries(e).forEach((e=>{let[t,n]=e;void 0===u[t]&&(s[t]?s[t].forEach((e=>{n?(0,i.p)("feat-"+t,[],void 0,e,r):(0,i.p)("block-"+t,[],void 0,e,r),(0,i.p)("rumresp-"+t,[Boolean(n)],void 0,e,r)})):n&&(0,i.p)("feat-"+t,[],void 0,void 0,r),u[t]=Boolean(n))})),Object.keys(s).forEach((e=>{void 0===u[e]&&(s[e]?.forEach((t=>(0,i.p)("rumresp-"+e,[!1],void 0,t,r))),u[e]=!1)})),(0,o.L)(t,a.D.pageViewEvent))}const u={}},2210:(e,t,r)=>{r.d(t,{X:()=>i});var n=Object.prototype.hasOwnProperty;function i(e,t,r){if(n.call(e,t))return e[t];var i=r();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(e,t,{value:i,writable:!0,enumerable:!1}),i}catch(e){}return e[t]=i,i}},1284:(e,t,r)=>{r.d(t,{D:()=>n});const n=(e,t)=>Object.entries(e||{}).map((e=>{let[r,n]=e;return t(r,n)}))},4351:(e,t,r)=>{r.d(t,{P:()=>o});var n=r(2177);const i=()=>{const e=new WeakSet;return(t,r)=>{if("object"==typeof r&&null!==r){if(e.has(r))return;e.add(r)}return r}};function o(e){try{return JSON.stringify(e,i())}catch(e){try{n.ee.emit("internal-error",[e])}catch(e){}}}},3960:(e,t,r)=>{r.d(t,{K:()=>a,b:()=>o});var n=r(3239);function i(){return"undefined"==typeof document||"complete"===document.readyState}function o(e,t){if(i())return e();(0,n.bP)("load",e,t)}function a(e){if(i())return e();(0,n.iz)("DOMContentLoaded",e)}},8632:(e,t,r)=>{r.d(t,{EZ:()=>u,Qy:()=>c,ce:()=>o,fP:()=>a,gG:()=>d,mF:()=>s});var n=r(7894),i=r(385);const o={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net"};function a(){return i._A.NREUM||(i._A.NREUM={}),void 0===i._A.newrelic&&(i._A.newrelic=i._A.NREUM),i._A.NREUM}function s(){let e=a();return e.o||(e.o={ST:i._A.setTimeout,SI:i._A.setImmediate,CT:i._A.clearTimeout,XHR:i._A.XMLHttpRequest,REQ:i._A.Request,EV:i._A.Event,PR:i._A.Promise,MO:i._A.MutationObserver,FETCH:i._A.fetch}),e}function c(e,t,r){let i=a();const o=i.initializedAgents||{},s=o[e]||{};return Object.keys(s).length||(s.initializedAt={ms:(0,n.z)(),date:new Date}),i.initializedAgents={...o,[e]:{...s,[r]:t}},i}function u(e,t){a()[e]=t}function d(){return function(){let e=a();const t=e.info||{};e.info={beacon:o.beacon,errorBeacon:o.errorBeacon,...t}}(),function(){let e=a();const t=e.init||{};e.init={...t}}(),s(),function(){let e=a();const t=e.loader_config||{};e.loader_config={...t}}(),a()}},7956:(e,t,r)=>{r.d(t,{N:()=>i});var n=r(3239);function i(e){let t=arguments.length>1&&void 0!==arguments[1]&&arguments[1],r=arguments.length>2?arguments[2]:void 0,i=arguments.length>3?arguments[3]:void 0;return void(0,n.iz)("visibilitychange",(function(){if(t)return void("hidden"==document.visibilityState&&e());e(document.visibilityState)}),r,i)}},1214:(e,t,r)=>{r.d(t,{em:()=>v,u5:()=>N,QU:()=>S,_L:()=>I,Gm:()=>L,Lg:()=>M,gy:()=>U,BV:()=>Q,Kf:()=>ee});var n=r(2177);const i="nr@original";var o=Object.prototype.hasOwnProperty,a=!1;function s(e,t){return e||(e=n.ee),r.inPlace=function(e,t,n,i,o){n||(n="");var a,s,c,u="-"===n.charAt(0);for(c=0;c 2?n-2:0),o=2;o {r(A[T],e,w),r(E[T],e,w)})),r(l._A,"fetch",y),t.on(y+"end",(function(e,r){var n=this;if(r){var i=r.headers.get("content-length");null!==i&&(n.rxSize=i),t.emit(y+"done",[null,r],n)}else t.emit(y+"done",[e],n)})),t}const O={},j=["pushState","replaceState"];function S(e){const t=function(e){return(e||n.ee).get("history")}(e);return!l.il||O[t.debugId]++||(O[t.debugId]=1,s(t).inPlace(window.history,j,"-")),t}var P=r(3239);const C={},R=["appendChild","insertBefore","replaceChild"];function I(e){const t=function(e){return(e||n.ee).get("jsonp")}(e);if(!l.il||C[t.debugId])return t;C[t.debugId]=!0;var r=s(t),i=/[?&](?:callback|cb)=([^&#]+)/,o=/(.*)\.([^.]+)/,a=/^(\w+)(\.|$)(.*)$/;function c(e,t){var r=e.match(a),n=r[1],i=r[3];return i?c(i,t[n]):t[n]}return r.inPlace(Node.prototype,R,"dom-"),t.on("dom-start",(function(e){!function(e){if(!e||"string"!=typeof e.nodeName||"script"!==e.nodeName.toLowerCase())return;if("function"!=typeof e.addEventListener)return;var n=(a=e.src,s=a.match(i),s?s[1]:null);var a,s;if(!n)return;var u=function(e){var t=e.match(o);if(t&&t.length>=3)return{key:t[2],parent:c(t[1],window)};return{key:e,parent:window}}(n);if("function"!=typeof u.parent[u.key])return;var d={};function f(){t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}function l(){t.emit("jsonp-error",[],d),t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}r.inPlace(u.parent,[u.key],"cb-",d),e.addEventListener("load",f,(0,P.m$)(!1)),e.addEventListener("error",l,(0,P.m$)(!1)),t.emit("new-jsonp",[e.src],d)}(e[0])})),t}var k=r(5763);const H={};function L(e){const t=function(e){return(e||n.ee).get("mutation")}(e);if(!l.il||H[t.debugId])return t;H[t.debugId]=!0;var r=s(t),i=k.Yu.MO;return i&&(window.MutationObserver=function(e){return this instanceof i?new i(r(e,"fn-")):i.apply(this,arguments)},MutationObserver.prototype=i.prototype),t}const z={};function M(e){const t=function(e){return(e||n.ee).get("promise")}(e);if(z[t.debugId])return t;z[t.debugId]=!0;var r=n.c,o=s(t),a=k.Yu.PR;return a&&function(){function e(r){var n=t.context(),i=o(r,"executor-",n,null,!1);const s=Reflect.construct(a,[i],e);return t.context(s).getCtx=function(){return n},s}l._A.Promise=e,Object.defineProperty(e,"name",{value:"Promise"}),e.toString=function(){return a.toString()},Object.setPrototypeOf(e,a),["all","race"].forEach((function(r){const n=a[r];e[r]=function(e){let i=!1;[...e||[]].forEach((e=>{this.resolve(e).then(a("all"===r),a(!1))}));const o=n.apply(this,arguments);return o;function a(e){return function(){t.emit("propagate",[null,!i],o,!1,!1),i=i||!e}}}})),["resolve","reject"].forEach((function(r){const n=a[r];e[r]=function(e){const r=n.apply(this,arguments);return e!==r&&t.emit("propagate",[e,!0],r,!1,!1),r}})),e.prototype=a.prototype;const n=a.prototype.then;a.prototype.then=function(){var e=this,i=r(e);i.promise=e;for(var a=arguments.length,s=new Array(a),c=0;c e())),t};function m(e,t){i.inPlace(t,["onreadystatechange"],"fn-",E)}function b(){var e=this,t=r.context(e);e.readyState>3&&!t.resolved&&(t.resolved=!0,r.emit("xhr-resolved",[],e)),i.inPlace(e,f,"fn-",E)}if(function(e,t){for(var r in e)t[r]=e[r]}(o,p),p.prototype=o.prototype,i.inPlace(p.prototype,J,"-xhr-",E),r.on("send-xhr-start",(function(e,t){m(e,t),function(e){h.push(e),a&&(y?y.then(A):u?u(A):(w=-w,x.data=w))}(t)})),r.on("open-xhr-start",m),a){var y=c&&c.resolve();if(!u&&!c){var w=1,x=document.createTextNode(w);new a(A).observe(x,{characterData:!0})}}else t.on("fn-end",(function(e){e[0]&&e[0].type===d||A()}));function A(){for(var e=0;e {r.d(t,{t:()=>n});const n=r(3325).D.ajax},6660:(e,t,r)=>{r.d(t,{A:()=>i,t:()=>n});const n=r(3325).D.jserrors,i="nr@seenError"},3081:(e,t,r)=>{r.d(t,{gF:()=>o,mY:()=>i,t9:()=>n,vz:()=>s,xS:()=>a});const n=r(3325).D.metrics,i="sm",o="cm",a="storeSupportabilityMetrics",s="storeEventMetrics"},4649:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageAction},7633:(e,t,r)=>{r.d(t,{Dz:()=>i,OJ:()=>a,qw:()=>o,t9:()=>n});const n=r(3325).D.pageViewEvent,i="firstbyte",o="domcontent",a="windowload"},9251:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageViewTiming},3614:(e,t,r)=>{r.d(t,{BST_RESOURCE:()=>i,END:()=>s,FEATURE_NAME:()=>n,FN_END:()=>u,FN_START:()=>c,PUSH_STATE:()=>d,RESOURCE:()=>o,START:()=>a});const n=r(3325).D.sessionTrace,i="bstResource",o="resource",a="-start",s="-end",c="fn"+a,u="fn"+s,d="pushState"},7836:(e,t,r)=>{r.d(t,{BODY:()=>A,CB_END:()=>E,CB_START:()=>u,END:()=>x,FEATURE_NAME:()=>i,FETCH:()=>_,FETCH_BODY:()=>v,FETCH_DONE:()=>m,FETCH_START:()=>p,FN_END:()=>c,FN_START:()=>s,INTERACTION:()=>l,INTERACTION_API:()=>d,INTERACTION_EVENTS:()=>o,JSONP_END:()=>b,JSONP_NODE:()=>g,JS_TIME:()=>T,MAX_TIMER_BUDGET:()=>a,REMAINING:()=>f,SPA_NODE:()=>h,START:()=>w,originalSetTimeout:()=>y});var n=r(5763);const i=r(3325).D.spa,o=["click","submit","keypress","keydown","keyup","change"],a=999,s="fn-start",c="fn-end",u="cb-start",d="api-ixn-",f="remaining",l="interaction",h="spaNode",g="jsonpNode",p="fetch-start",m="fetch-done",v="fetch-body-",b="jsonp-end",y=n.Yu.ST,w="-start",x="-end",A="-body",E="cb"+x,T="jsTime",_="fetch"},5938:(e,t,r)=>{r.d(t,{W:()=>o});var n=r(5763),i=r(2177);class o{constructor(e,t,r){this.agentIdentifier=e,this.aggregator=t,this.ee=i.ee.get(e,(0,n.OP)(this.agentIdentifier).isolatedBacklog),this.featureName=r,this.blocked=!1}}},9144:(e,t,r)=>{r.d(t,{j:()=>m});var n=r(3325),i=r(5763),o=r(5546),a=r(2177),s=r(7894),c=r(8e3),u=r(3960),d=r(385),f=r(50),l=r(3081),h=r(8632);function g(){const e=(0,h.gG)();["setErrorHandler","finished","addToTrace","inlineHit","addRelease","addPageAction","setCurrentRouteName","setPageViewName","setCustomAttribute","interaction","noticeError","setUserId"].forEach((t=>{e[t]=function(){for(var r=arguments.length,n=new Array(r),i=0;i 1?r-1:0),i=1;i {e.exposed&&e.api[t]&&o.push(e.api[t](...n))})),o.length>1?o:o[0]}(t,...n)}}))}var p=r(2587);function m(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{},m=arguments.length>2?arguments[2]:void 0,v=arguments.length>3?arguments[3]:void 0,{init:b,info:y,loader_config:w,runtime:x={loaderType:m},exposed:A=!0}=t;const E=(0,h.gG)();y||(b=E.init,y=E.info,w=E.loader_config),(0,i.Dg)(e,b||{}),(0,i.GE)(e,w||{}),(0,i.sU)(e,x),y.jsAttributes??={},d.v6&&(y.jsAttributes.isWorker=!0),(0,i.CX)(e,y),g();const T=function(e,t){t||(0,c.R)(e,"api");const h={};var g=a.ee.get(e),p=g.get("tracer"),m="api-",v=m+"ixn-";function b(t,r,n,o){const a=(0,i.C5)(e);return null===r?delete a.jsAttributes[t]:(0,i.CX)(e,{...a,jsAttributes:{...a.jsAttributes,[t]:r}}),x(m,n,!0,o||null===r?"session":void 0)(t,r)}function y(){}["setErrorHandler","finished","addToTrace","inlineHit","addRelease"].forEach((e=>h[e]=x(m,e,!0,"api"))),h.addPageAction=x(m,"addPageAction",!0,n.D.pageAction),h.setCurrentRouteName=x(m,"routeName",!0,n.D.spa),h.setPageViewName=function(t,r){if("string"==typeof t)return"/"!==t.charAt(0)&&(t="/"+t),(0,i.OP)(e).customTransaction=(r||"http://custom.transaction")+t,x(m,"setPageViewName",!0)()},h.setCustomAttribute=function(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2];if("string"==typeof e){if(["string","number"].includes(typeof t)||null===t)return b(e,t,"setCustomAttribute",r);(0,f.Z)("Failed to execute setCustomAttribute.\nNon-null value must be a string or number type, but a type of was provided."))}else(0,f.Z)("Failed to execute setCustomAttribute.\nName must be a string type, but a type of was provided."))},h.setUserId=function(e){if("string"==typeof e||null===e)return b("enduser.id",e,"setUserId",!0);(0,f.Z)("Failed to execute setUserId.\nNon-null value must be a string type, but a type of was provided."))},h.interaction=function(){return(new y).get()};var w=y.prototype={createTracer:function(e,t){var r={},i=this,a="function"==typeof t;return(0,o.p)(v+"tracer",[(0,s.z)(),e,r],i,n.D.spa,g),function(){if(p.emit((a?"":"no-")+"fn-start",[(0,s.z)(),i,a],r),a)try{return t.apply(this,arguments)}catch(e){throw p.emit("fn-err",[arguments,this,"string"==typeof e?new Error(e):e],r),e}finally{p.emit("fn-end",[(0,s.z)()],r)}}}};function x(e,t,r,i){return function(){return(0,o.p)(l.xS,["API/"+t+"/called"],void 0,n.D.metrics,g),i&&(0,o.p)(e+t,[(0,s.z)(),...arguments],r?null:this,i,g),r?void 0:this}}function A(){r.e(439).then(r.bind(r,7438)).then((t=>{let{setAPI:r}=t;r(e),(0,c.L)(e,"api")})).catch((()=>(0,f.Z)("Downloading runtime APIs failed...")))}return["actionText","setName","setAttribute","save","ignore","onEnd","getContext","end","get"].forEach((e=>{w[e]=x(v,e,void 0,n.D.spa)})),h.noticeError=function(e,t){"string"==typeof e&&(e=new Error(e)),(0,o.p)(l.xS,["API/noticeError/called"],void 0,n.D.metrics,g),(0,o.p)("err",[e,(0,s.z)(),!1,t],void 0,n.D.jserrors,g)},d.il?(0,u.b)((()=>A()),!0):A(),h}(e,v);return(0,h.Qy)(e,T,"api"),(0,h.Qy)(e,A,"exposed"),(0,h.EZ)("activatedFeatures",p.T),T}},3325:(e,t,r)=>{r.d(t,{D:()=>n,p:()=>i});const n={ajax:"ajax",jserrors:"jserrors",metrics:"metrics",pageAction:"page_action",pageViewEvent:"page_view_event",pageViewTiming:"page_view_timing",sessionReplay:"session_replay",sessionTrace:"session_trace",spa:"spa"},i={[n.pageViewEvent]:1,[n.pageViewTiming]:2,[n.metrics]:3,[n.jserrors]:4,[n.ajax]:5,[n.sessionTrace]:6,[n.pageAction]:7,[n.spa]:8,[n.sessionReplay]:9}}},n={};function i(e){var t=n[e];if(void 0!==t)return t.exports;var o=n[e]={exports:{}};return r[e](o,o.exports,i),o.exports}i.m=r,i.d=(e,t)=>{for(var r in t)i.o(t,r)&&!i.o(e,r)&&Object.defineProperty(e,r,{enumerable:!0,get:t[r]})},i.f={},i.e=e=>Promise.all(Object.keys(i.f).reduce(((t,r)=>(i.f[r](e,t),t)),[])),i.u=e=>(({78:"page_action-aggregate",147:"metrics-aggregate",242:"session-manager",317:"jserrors-aggregate",348:"page_view_timing-aggregate",412:"lazy-feature-loader",439:"async-api",538:"recorder",590:"session_replay-aggregate",675:"compressor",733:"session_trace-aggregate",786:"page_view_event-aggregate",873:"spa-aggregate",898:"ajax-aggregate"}[e]||e)+"."+{78:"ac76d497",147:"3dc53903",148:"1a20d5fe",242:"2a64278a",317:"49e41428",348:"bd6de33a",412:"2f55ce66",439:"30bd804e",538:"1b18459f",590:"cf0efb30",675:"ae9f91a8",733:"83105561",786:"06482edd",860:"03a8b7a5",873:"e6b09d52",898:"998ef92b"}[e]+"-1.236.0.min.js"),i.o=(e,t)=>Object.prototype.hasOwnProperty.call(e,t),e={},t="NRBA:",i.l=(r,n,o,a)=>{if(e[r])e[r].push(n);else{var s,c;if(void 0!==o)for(var u=document.getElementsByTagName("script"),d=0;d {s.onerror=s.onload=null,clearTimeout(h);var i=e[r];if(delete e[r],s.parentNode&&s.parentNode.removeChild(s),i&&i.forEach((e=>e(n))),t)return t(n)},h=setTimeout(l.bind(null,void 0,{type:"timeout",target:s}),12e4);s.onerror=l.bind(null,s.onerror),s.onload=l.bind(null,s.onload),c&&document.head.appendChild(s)}},i.r=e=>{"undefined"!=typeof Symbol&&Symbol.toStringTag&&Object.defineProperty(e,Symbol.toStringTag,{value:"Module"}),Object.defineProperty(e,"__esModule",{value:!0})},i.j=364,i.p="https://js-agent.newrelic.com/",(()=>{var e={364:0,953:0};i.f.j=(t,r)=>{var n=i.o(e,t)?e[t]:void 0;if(0!==n)if(n)r.push(n[2]);else{var o=new Promise(((r,i)=>n=e[t]=[r,i]));r.push(n[2]=o);var a=i.p+i.u(t),s=new Error;i.l(a,(r=>{if(i.o(e,t)&&(0!==(n=e[t])&&(e[t]=void 0),n)){var o=r&&("load"===r.type?"missing":r.type),a=r&&r.target&&r.target.src;s.message="Loading chunk "+t+" failed.\n("+o+": "+a+")",s.name="ChunkLoadError",s.type=o,s.request=a,n[1](s)}}),"chunk-"+t,t)}};var t=(t,r)=>{var n,o,[a,s,c]=r,u=0;if(a.some((t=>0!==e[t]))){for(n in s)i.o(s,n)&&(i.m[n]=s[n]);if(c)c(i)}for(t&&t(r);u {i.r(o);var e=i(3325),t=i(5763);const r=Object.values(e.D);function n(e){const n={};return r.forEach((r=>{n[r]=function(e,r){return!1!==(0,t.Mt)(r,"".concat(e,".enabled"))}(r,e)})),n}var a=i(9144);var s=i(5546),c=i(385),u=i(8e3),d=i(5938),f=i(3960),l=i(50);class h extends d.W{constructor(e,t,r){let n=!(arguments.length>3&&void 0!==arguments[3])||arguments[3];super(e,t,r),this.auto=n,this.abortHandler,this.featAggregate,this.onAggregateImported,n&&(0,u.R)(e,r)}importAggregator(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:{};if(this.featAggregate||!this.auto)return;const r=c.il&&!0===(0,t.Mt)(this.agentIdentifier,"privacy.cookies_enabled");let n;this.onAggregateImported=new Promise((e=>{n=e}));const o=async()=>{let t;try{if(r){const{setupAgentSession:e}=await Promise.all([i.e(860),i.e(242)]).then(i.bind(i,3228));t=e(this.agentIdentifier)}}catch(e){(0,l.Z)("A problem occurred when starting up session manager. This page will not start or extend any session.",e)}try{if(!this.shouldImportAgg(this.featureName,t))return void(0,u.L)(this.agentIdentifier,this.featureName);const{lazyFeatureLoader:r}=await i.e(412).then(i.bind(i,8582)),{Aggregate:o}=await r(this.featureName,"aggregate");this.featAggregate=new o(this.agentIdentifier,this.aggregator,e),n(!0)}catch(e){(0,l.Z)("Downloading and initializing ".concat(this.featureName," failed..."),e),this.abortHandler?.(),n(!1)}};c.il?(0,f.b)((()=>o()),!0):o()}shouldImportAgg(r,n){return r!==e.D.sessionReplay||!1!==(0,t.Mt)(this.agentIdentifier,"session_trace.enabled")&&(!!n?.isNew||!!n?.state.sessionReplay)}}var g=i(7633),p=i(7894);class m extends h{static featureName=g.t9;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];if(super(r,n,g.t9,i),("undefined"==typeof PerformanceNavigationTiming||c.Tt)&&"undefined"!=typeof PerformanceTiming){const n=(0,t.OP)(r);n[g.Dz]=Math.max(Date.now()-n.offset,0),(0,f.K)((()=>n[g.qw]=Math.max((0,p.z)()-n[g.Dz],0))),(0,f.b)((()=>{const t=(0,p.z)();n[g.OJ]=Math.max(t-n[g.Dz],0),(0,s.p)("timing",["load",t],void 0,e.D.pageViewTiming,this.ee)}))}this.importAggregator()}}var v=i(1117),b=i(1284);class y extends v.w{constructor(e){super(e),this.aggregatedData={}}store(e,t,r,n,i){var o=this.getBucket(e,t,r,i);return o.metrics=function(e,t){t||(t={count:0});return t.count+=1,(0,b.D)(e,(function(e,r){t[e]=w(r,t[e])})),t}(n,o.metrics),o}merge(e,t,r,n,i){var o=this.getBucket(e,t,n,i);if(o.metrics){var a=o.metrics;a.count+=r.count,(0,b.D)(r,(function(e,t){if("count"!==e){var n=a[e],i=r[e];i&&!i.c?a[e]=w(i.t,n):a[e]=function(e,t){if(!t)return e;t.c||(t=x(t.t));return t.min=Math.min(e.min,t.min),t.max=Math.max(e.max,t.max),t.t+=e.t,t.sos+=e.sos,t.c+=e.c,t}(i,a[e])}}))}else o.metrics=r}storeMetric(e,t,r,n){var i=this.getBucket(e,t,r);return i.stats=w(n,i.stats),i}getBucket(e,t,r,n){this.aggregatedData[e]||(this.aggregatedData[e]={});var i=this.aggregatedData[e][t];return i||(i=this.aggregatedData[e][t]={params:r||{}},n&&(i.custom=n)),i}get(e,t){return t?this.aggregatedData[e]&&this.aggregatedData[e][t]:this.aggregatedData[e]}take(e){for(var t={},r="",n=!1,i=0;i t.max&&(t.max=e),e 2&&void 0!==arguments[2])||arguments[2];super(e,r,j.t,n),c.il&&((0,t.OP)(e).initHidden=Boolean("hidden"===document.visibilityState),(0,N.N)((()=>(0,s.p)("docHidden",[(0,p.z)()],void 0,j.t,this.ee)),!0),(0,O.bP)("pagehide",(()=>(0,s.p)("winPagehide",[(0,p.z)()],void 0,j.t,this.ee))),this.importAggregator())}}var P=i(3081);class C extends h{static featureName=P.t9;constructor(e,t){let r=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(e,t,P.t9,r),this.importAggregator()}}var R,I=i(2210),k=i(1214),H=i(2177),L={};try{R=localStorage.getItem("__nr_flags").split(","),console&&"function"==typeof console.log&&(L.console=!0,-1!==R.indexOf("dev")&&(L.dev=!0),-1!==R.indexOf("nr_dev")&&(L.nrDev=!0))}catch(e){}function z(e){try{L.console&&z(e)}catch(e){}}L.nrDev&&H.ee.on("internal-error",(function(e){z(e.stack)})),L.dev&&H.ee.on("fn-err",(function(e,t,r){z(r.stack)})),L.dev&&(z("NR AGENT IN DEVELOPMENT MODE"),z("flags: "+(0,b.D)(L,(function(e,t){return e})).join(", ")));var M=i(6660);class B extends h{static featureName=M.t;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(r,n,M.t,i),this.skipNext=0;try{this.removeOnAbort=new AbortController}catch(e){}const o=this;o.ee.on("fn-start",(function(e,t,r){o.abortHandler&&(o.skipNext+=1)})),o.ee.on("fn-err",(function(t,r,n){o.abortHandler&&!n[M.A]&&((0,I.X)(n,M.A,(function(){return!0})),this.thrown=!0,(0,s.p)("err",[n,(0,p.z)()],void 0,e.D.jserrors,o.ee))})),o.ee.on("fn-end",(function(){o.abortHandler&&!this.thrown&&o.skipNext>0&&(o.skipNext-=1)})),o.ee.on("internal-error",(function(t){(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,o.ee)})),this.origOnerror=c._A.onerror,c._A.onerror=this.onerrorHandler.bind(this),c._A.addEventListener("unhandledrejection",(t=>{const r=function(e){let t="Unhandled Promise Rejection: ";if(e instanceof Error)try{return e.message=t+e.message,e}catch(t){return e}if(void 0===e)return new Error(t);try{return new Error(t+(0,D.P)(e))}catch(e){return new Error(t)}}(t.reason);(0,s.p)("err",[r,(0,p.z)(),!1,{unhandledPromiseRejection:1}],void 0,e.D.jserrors,this.ee)}),(0,O.m$)(!1,this.removeOnAbort?.signal)),(0,k.gy)(this.ee),(0,k.BV)(this.ee),(0,k.em)(this.ee),(0,t.OP)(r).xhrWrappable&&(0,k.Kf)(this.ee),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}onerrorHandler(t,r,n,i,o){"function"==typeof this.origOnerror&&this.origOnerror(...arguments);try{this.skipNext?this.skipNext-=1:(0,s.p)("err",[o||new F(t,r,n),(0,p.z)()],void 0,e.D.jserrors,this.ee)}catch(t){try{(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,this.ee)}catch(e){}}return!1}}function F(e,t,r){this.message=e||"Uncaught error with no additional information",this.sourceURL=t,this.line=r}let U=1;const q="nr@id";function G(e){const t=typeof e;return!e||"object"!==t&&"function"!==t?-1:e===c._A?0:(0,I.X)(e,q,(function(){return U++}))}function V(e){if("string"==typeof e&&e.length)return e.length;if("object"==typeof e){if("undefined"!=typeof ArrayBuffer&&e instanceof ArrayBuffer&&e.byteLength)return e.byteLength;if("undefined"!=typeof Blob&&e instanceof Blob&&e.size)return e.size;if(!("undefined"!=typeof FormData&&e instanceof FormData))try{return(0,D.P)(e).length}catch(e){return}}}var X=i(7243);class W{constructor(e){this.agentIdentifier=e,this.generateTracePayload=this.generateTracePayload.bind(this),this.shouldGenerateTrace=this.shouldGenerateTrace.bind(this)}generateTracePayload(e){if(!this.shouldGenerateTrace(e))return null;var r=(0,t.DL)(this.agentIdentifier);if(!r)return null;var n=(r.accountID||"").toString()||null,i=(r.agentID||"").toString()||null,o=(r.trustKey||"").toString()||null;if(!n||!i)return null;var a=(0,_.M)(),s=(0,_.Ht)(),c=Date.now(),u={spanId:a,traceId:s,timestamp:c};return(e.sameOrigin||this.isAllowedOrigin(e)&&this.useTraceContextHeadersForCors())&&(u.traceContextParentHeader=this.generateTraceContextParentHeader(a,s),u.traceContextStateHeader=this.generateTraceContextStateHeader(a,c,n,i,o)),(e.sameOrigin&&!this.excludeNewrelicHeader()||!e.sameOrigin&&this.isAllowedOrigin(e)&&this.useNewrelicHeaderForCors())&&(u.newrelicHeader=this.generateTraceHeader(a,s,c,n,i,o)),u}generateTraceContextParentHeader(e,t){return"00-"+t+"-"+e+"-01"}generateTraceContextStateHeader(e,t,r,n,i){return i+"@nr=0-1-"+r+"-"+n+"-"+e+"----"+t}generateTraceHeader(e,t,r,n,i,o){if(!("function"==typeof c._A?.btoa))return null;var a={v:[0,1],d:{ty:"Browser",ac:n,ap:i,id:e,tr:t,ti:r}};return o&&n!==o&&(a.d.tk=o),btoa((0,D.P)(a))}shouldGenerateTrace(e){return this.isDtEnabled()&&this.isAllowedOrigin(e)}isAllowedOrigin(e){var r=!1,n={};if((0,t.Mt)(this.agentIdentifier,"distributed_tracing")&&(n=(0,t.P_)(this.agentIdentifier).distributed_tracing),e.sameOrigin)r=!0;else if(n.allowed_origins instanceof Array)for(var i=0;i 2&&void 0!==arguments[2])||arguments[2];super(r,n,Z.t,i),(0,t.OP)(r).xhrWrappable&&(this.dt=new W(r),this.handler=(e,t,r,n)=>(0,s.p)(e,t,r,n,this.ee),(0,k.u5)(this.ee),(0,k.Kf)(this.ee),function(r,n,i,o){function a(e){var t=this;t.totalCbs=0,t.called=0,t.cbTime=0,t.end=E,t.ended=!1,t.xhrGuids={},t.lastSize=null,t.loadCaptureCalled=!1,t.params=this.params||{},t.metrics=this.metrics||{},e.addEventListener("load",(function(r){_(t,e)}),(0,O.m$)(!1)),c.IF||e.addEventListener("progress",(function(e){t.lastSize=e.loaded}),(0,O.m$)(!1))}function s(e){this.params={method:e[0]},T(this,e[1]),this.metrics={}}function u(e,n){var i=(0,t.DL)(r);i.xpid&&this.sameOrigin&&n.setRequestHeader("X-NewRelic-ID",i.xpid);var a=o.generateTracePayload(this.parsedOrigin);if(a){var s=!1;a.newrelicHeader&&(n.setRequestHeader("newrelic",a.newrelicHeader),s=!0),a.traceContextParentHeader&&(n.setRequestHeader("traceparent",a.traceContextParentHeader),a.traceContextStateHeader&&n.setRequestHeader("tracestate",a.traceContextStateHeader),s=!0),s&&(this.dt=a)}}function d(e,t){var r=this.metrics,i=e[0],o=this;if(r&&i){var a=V(i);a&&(r.txSize=a)}this.startTime=(0,p.z)(),this.listener=function(e){try{"abort"!==e.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==e.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof t.onload)&&"function"==typeof o.end)&&o.end(t)}catch(e){try{n.emit("internal-error",[e])}catch(e){}}};for(var s=0;s 1?e[1]=i:e.push(i)}else e[0]&&e[0].headers&&s(e[0].headers,n)&&(this.dt=n);function s(e,t){var r=!1;return t.newrelicHeader&&(e.set("newrelic",t.newrelicHeader),r=!0),t.traceContextParentHeader&&(e.set("traceparent",t.traceContextParentHeader),t.traceContextStateHeader&&e.set("tracestate",t.traceContextStateHeader),r=!0),r}}function x(e,t){this.params={},this.metrics={},this.startTime=(0,p.z)(),this.dt=t,e.length>=1&&(this.target=e[0]),e.length>=2&&(this.opts=e[1]);var r,n=this.opts||{},i=this.target;"string"==typeof i?r=i:"object"==typeof i&&i instanceof Y?r=i.url:c._A?.URL&&"object"==typeof i&&i instanceof URL&&(r=i.href),T(this,r);var o=(""+(i&&i instanceof Y&&i.method||n.method||"GET")).toUpperCase();this.params.method=o,this.txSize=V(n.body)||0}function A(t,r){var n;this.endTime=(0,p.z)(),this.params||(this.params={}),this.params.status=r?r.status:0,"string"==typeof this.rxSize&&this.rxSize.length>0&&(n=+this.rxSize);var o={txSize:this.txSize,rxSize:n,duration:(0,p.z)()-this.startTime};i("xhr",[this.params,o,this.startTime,this.endTime,"fetch"],this,e.D.ajax)}function E(t){var r=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(var o=0;o 2&&void 0!==arguments[2])||arguments[2];super(e,t,we.t,r),this.importAggregator()}}new class{constructor(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:(0,_.ky)(16);c._A?(this.agentIdentifier=t,this.sharedAggregator=new y({agentIdentifier:this.agentIdentifier}),this.features={},this.desiredFeatures=new Set(e.features||[]),this.desiredFeatures.add(m),Object.assign(this,(0,a.j)(this.agentIdentifier,e,e.loaderType||"agent")),this.start()):(0,l.Z)("Failed to initial the agent. Could not determine the runtime environment.")}get config(){return{info:(0,t.C5)(this.agentIdentifier),init:(0,t.P_)(this.agentIdentifier),loader_config:(0,t.DL)(this.agentIdentifier),runtime:(0,t.OP)(this.agentIdentifier)}}start(){const t="features";try{const r=n(this.agentIdentifier),i=[...this.desiredFeatures];i.sort(((t,r)=>e.p[t.featureName]-e.p[r.featureName])),i.forEach((t=>{if(r[t.featureName]||t.featureName===e.D.pageViewEvent){const n=function(t){switch(t){case e.D.ajax:return[e.D.jserrors];case e.D.sessionTrace:return[e.D.ajax,e.D.pageViewEvent];case e.D.sessionReplay:return[e.D.sessionTrace];case e.D.pageViewTiming:return[e.D.pageViewEvent];default:return[]}}(t.featureName);n.every((e=>r[e]))||(0,l.Z)("".concat(t.featureName," is enabled but one or more dependent features has been disabled (").concat((0,D.P)(n),"). This may cause unintended consequences or missing data...")),this.features[t.featureName]=new t(this.agentIdentifier,this.sharedAggregator)}})),(0,T.Qy)(this.agentIdentifier,this.features,t)}catch(e){(0,l.Z)("Failed to initialize all enabled instrument classes (agent aborted) -",e);for(const e in this.features)this.features[e].abortHandler?.();const r=(0,T.fP)();return delete r.initializedAgents[this.agentIdentifier]?.api,delete r.initializedAgents[this.agentIdentifier]?.[t],delete this.sharedAggregator,r.ee?.abort(),delete r.ee?.get(this.agentIdentifier),!1}}}({features:[J,m,S,class extends h{static featureName=oe;constructor(t,r){if(super(t,r,oe,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;const n=this.ee;let i;(0,k.QU)(n),this.eventsEE=(0,k.em)(n),this.eventsEE.on(se,(function(e,t){this.bstStart=(0,p.z)()})),this.eventsEE.on(ae,(function(t,r){(0,s.p)("bst",[t[0],r,this.bstStart,(0,p.z)()],void 0,e.D.sessionTrace,n)})),n.on(ce+ne,(function(e){this.time=(0,p.z)(),this.startPath=location.pathname+location.hash})),n.on(ce+ie,(function(t){(0,s.p)("bstHist",[location.pathname+location.hash,this.startPath,this.time],void 0,e.D.sessionTrace,n)}));try{i=new PerformanceObserver((t=>{const r=t.getEntries();(0,s.p)(te,[r],void 0,e.D.sessionTrace,n)})),i.observe({type:re,buffered:!0})}catch(e){}this.importAggregator({resourceObserver:i})}},C,xe,B,class extends h{static featureName=de;constructor(e,r){if(super(e,r,de,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;if(!(0,t.OP)(e).xhrWrappable)return;try{this.removeOnAbort=new AbortController}catch(e){}let n,i=0;const o=this.ee.get("tracer"),a=(0,k._L)(this.ee),s=(0,k.Lg)(this.ee),u=(0,k.BV)(this.ee),d=(0,k.Kf)(this.ee),f=this.ee.get("events"),l=(0,k.u5)(this.ee),h=(0,k.QU)(this.ee),g=(0,k.Gm)(this.ee);function m(e,t){h.emit("newURL",[""+window.location,t])}function v(){i++,n=window.location.hash,this[ve]=(0,p.z)()}function b(){i--,window.location.hash!==n&&m(0,!0);var e=(0,p.z)();this[pe]=~~this[pe]+e-this[ve],this[ye]=e}function y(e,t){e.on(t,(function(){this[t]=(0,p.z)()}))}this.ee.on(ve,v),s.on(be,v),a.on(be,v),this.ee.on(ye,b),s.on(ge,b),a.on(ge,b),this.ee.buffer([ve,ye,"xhr-resolved"],this.featureName),f.buffer([ve],this.featureName),u.buffer(["setTimeout"+le,"clearTimeout"+fe,ve],this.featureName),d.buffer([ve,"new-xhr","send-xhr"+fe],this.featureName),l.buffer([me+fe,me+"-done",me+he+fe,me+he+le],this.featureName),h.buffer(["newURL"],this.featureName),g.buffer([ve],this.featureName),s.buffer(["propagate",be,ge,"executor-err","resolve"+fe],this.featureName),o.buffer([ve,"no-"+ve],this.featureName),a.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"],this.featureName),y(l,me+fe),y(l,me+"-done"),y(a,"new-jsonp"),y(a,"jsonp-end"),y(a,"cb-start"),h.on("pushState-end",m),h.on("replaceState-end",m),window.addEventListener("hashchange",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("load",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("popstate",(function(){m(0,i>1)}),(0,O.m$)(!0,this.removeOnAbort?.signal)),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}],loaderType:"spa"})})(),window.NRBA=o})(); window.jQuery || document.write(' ') CKEDITOR_BASEPATH='https://f1000research.com/js/vendor/ckeditor/' window.reactTheme = 'research'; window.MathJax = { CommonHTML: { linebreaks: { automatic: true } }, 'HTML-CSS': { linebreaks: { automatic: true } }, SVG: { linebreaks: { automatic: true } }, AuthorInit: function() { MathJax.Hub.Register.MessageHook('End Process', function () { let timeout = false; // holder for timeout id const delay = 250; // delay after event is "complete" to run callback const reflowMath = function() { const dispFormulas = document.querySelectorAll('.disp-formula.panel'); if (!dispFormulas) { return; } for (const dispFormula of dispFormulas) { const child = dispFormula.querySelector('.MathJax_Preview').nextSibling.firstChild; const isMultiline = MathJax.Hub.getAllJax(dispFormula)[0].root.isMultiline; if (dispFormula.offsetWidth < child.offsetWidth || isMultiline) { MathJax.Hub.Queue(['Rerender', MathJax.Hub, dispFormula]); } } }; window.addEventListener('resize', function() { clearTimeout(timeout); // clear the timeout timeout = setTimeout(reflowMath, delay); // start timing for event "completion" }); }); }, }; if (window.location.hash == '#_=_'){ window.location = window.location.href.split('#')[0] } !function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function() {n.callMethod? n.callMethod.apply(n,arguments):n.queue.push(arguments)} ;if(!f._fbq)f._fbq=n; n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '1641728616063202'); fbq('track', "PixelInitialized", {}); (function(h,o,t,j,a,r){ h.hj=h.hj||function(){(h.hj.q=h.hj.q||[]).push(arguments)}; h._hjSettings={hjid:2318163,hjsv:6}; a=o.getElementsByTagName('head')[0]; r=o.createElement('script');r.async=1; r.src=t+h._hjSettings.hjid+j+h._hjSettings.hjsv; a.appendChild(r); })(window,document,'https://static.hotjar.com/c/hotjar-','.js?sv='); search file_upload Submit your research search menu close search Browse Gateways & Collections How to Publish Submit your Research My Submissions Article Guidelines Article Guidelines (New Versions) Open Data, Software and Code Guidelines Open Data and Accessible Source Materials Guidelines (HSS) Open Data, Software and Code Guidelines (PSE) Prepublication Checks Production Process Posters and Slides Guidelines Document Guidelines Article Processing Charges Peer Review Finding Article Reviewers About How it Works For Reviewers Our Advisors Policies Glossary FAQs For Developers Newsroom Contact My Research Submissions Content and Tracking Alerts My Details Sign In file_upload Submit your research { "@context": "https://schema.org", "@type": "ScholarlyArticle", "mainEntityOfPage": { "@type": "WebPage", "@id": "https://f1000research.com/articles/15-120" }, "headline": "From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation", "datePublished": "2026-01-27T03:32:27", "dateModified": "2026-01-27T03:32:27", "author": [ { "@type": "Person", "name": "Anatoliy V Zubritskiy" }, { "@type": "Person", "name": "Yulia A. Medvedeva" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": "The functional characterization of long non-coding RNAs (lncRNA) has been disproportionately shaped by the paradigm of cytoplasmic miRNA sponging, a model that, while valid for many transcripts, has overshadowed a more fundamental and impactful role. This opinion article argues for a critical conceptual shift, positing that the most potent role of many lncRNAs is not as competitive sponges, but as primary architects and scaffolds of the epigenetic landscape. The prevailing focus on the cytoplasm has created diagnostic and therapeutic blind spots. We contend that deliberately recentering the narrative around lncRNAs as nuclear scaffolds and specificity factors for chromatin-modifying complexes is essential for identifying precise disease biomarkers and developing the next generation of targeted epigenetic therapies." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/15-120", "name": "From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation" } } ] } Home Browse From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Zubritskiy AV and Medvedeva YA. From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :120 ( https://doi.org/10.12688/f1000research.175368.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Opinion Article From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation [version 1; peer review: 2 approved with reservations] Anatoliy V Zubritskiy 1 , Yulia A. Medvedeva https://orcid.org/0000-0002-7587-1666 1 Anatoliy V Zubritskiy 1 , Yulia A. Medvedeva https://orcid.org/0000-0002-7587-1666 1 PUBLISHED 27 Jan 2026 Author details Author details 1 Skryabin Institute of Bioengineering, Research Centre of Biotechnology, Mosocw, 117312, Russian Federation Anatoliy V Zubritskiy Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing Yulia A. Medvedeva Roles: Conceptualization, Funding Acquisition, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Cell & Molecular Biology gateway. Abstract The functional characterization of long non-coding RNAs (lncRNA) has been disproportionately shaped by the paradigm of cytoplasmic miRNA sponging, a model that, while valid for many transcripts, has overshadowed a more fundamental and impactful role. This opinion article argues for a critical conceptual shift, positing that the most potent role of many lncRNAs is not as competitive sponges, but as primary architects and scaffolds of the epigenetic landscape. The prevailing focus on the cytoplasm has created diagnostic and therapeutic blind spots. We contend that deliberately recentering the narrative around lncRNAs as nuclear scaffolds and specificity factors for chromatin-modifying complexes is essential for identifying precise disease biomarkers and developing the next generation of targeted epigenetic therapies. READ ALL READ LESS Keywords long non-coding RNA (lncRNA); epigenetics; chromatin regulation; miRNA sponge; RNA-chromatin interaction Corresponding Author(s) Yulia A. Medvedeva ( [email protected] ) Close Corresponding author: Yulia A. Medvedeva Competing interests: No competing interests were disclosed. Grant information: This work was partially supported by RSF grant number 23-14-00371 to Y.A.M. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2026 Zubritskiy AV and Medvedeva YA. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Zubritskiy AV and Medvedeva YA. From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :120 ( https://doi.org/10.12688/f1000research.175368.1 ) First published: 27 Jan 2026, 15 :120 ( https://doi.org/10.12688/f1000research.175368.1 ) Latest published: 27 Jan 2026, 15 :120 ( https://doi.org/10.12688/f1000research.175368.1 ) The Dominant narrative and the overlooked reality The human genome transcribes a vast repertoire of long non-coding RNAs (lncRNAs) which is comparable in number to protein-coding genes. 1 Despite challenges in functional annotation due to their low and tissue-specific expression, unique regulatory patterns, 2 and variable evolutionary conservation, 3 other characteristics such as conserved synteny, short sequence fragments, and secondary structures suggest significant biological potential. 4 The majority of lncRNAs interact with chromatin and are implicated in the epigenetic control of specific genomic loci and higher-order chromosome organization. 5 – 7 This has positioned them as intrinsic regulators of the nuclear landscape. However, the explosion of research into these molecules has been dominated by a compelling but narrow narrative: the role of lncRNAs as cytoplasmic miRNA sponges. This mechanism, exemplified by A1BG-AS1 sequestering miR- 485-5p 8 or FGD5-AS1 binding miR-195, 9 is mechanistically tangible but has overshadowed its nuclear and epigenetic functions. The quantitative bias is stark, with PubMed searches for “lncRNA and miRNA” (23,000+ results) vastly outnumbering those for “lncRNA and epigenetics” (6,500 results). This disparity signifies a profound conceptual imbalance that keeps the field’s native disproportionately anchored in the cytoplasm. It is not merely academic; it signifies a profound conceptual bias. In our collective focus on these cytoplasmic interactions, we systematically undervalued a more fundamental function: the role of lncRNAs as master regulators of the epigenetic landscape. This oversight is not due to a lack of evidence—the data are robust and detailed—but rather to a failure of narrative prioritization. It is time to capture this imbalance and recognize lncRNAs as central, specific, and dynamic architects of chromatin structure and genomic output. The functional annotation challenge: A roadmap for epigenetic lncRNAs Deciphering the epigenetic function of an lncRNA is a multi-layered endeavors that begin with the foundational step of confirming its non-coding status through integrated transcriptomic and proteomic analyses. 10 Once established, this investigation pivots the nucleus. The next critical phase is the mapping of the effects of experimental lncRNA perturbation 5 and its direct physical contact with the genome, 11 ideally distinguishing between various binding modalities such as triplex formation, R-loop association, or protein-mediated interactions. Computational predictions can guide the hypothesis generation for these targets. However, mere co-location with chromatin is insufficient. True functional validation requires linking this physical occupancy to a tangible epigenetic outcome, demonstrating that lncRNA perturbation directly alters local histone modifications (e.g., H3K27me3), DNA methylation patterns, or the recruitment of specific chromatin-modifying complexes. Furthermore, because the function is often dictated by the secondary structure rather than the primary sequence, resolving its higher order architecture is essential. Ultimately, a conclusive mechanistic model can only be achieved by integrating these disparate data streams—genomic binding maps, epigenetic state changes, structural insights, and transcriptional outputs—to explain how e lncRNAs act as precise scaffolds, guiding epigenetic machinery to specific loci to regulate gene expression. This rigorous roadmap highlights why epigenetic annotation is difficult, but its necessity is precisely what makes the conclusions useful. The compelling epigenetic case: Beyond cytoplasmic noise Our research and a thorough reading of the literature reveal a consistent and underappreciated theme: the most functionally significant lncRNAs are those that operate in the nucleus, directly interfacing with chromatin machinery. We consider the case of SPRY4-AS1 (AC005592.2). This lncRNA is transcribed from a super-enhancer region, a dense cluster of regulatory elements that define cell identity by forming long-range chromatin loops. 12 The lncRNA produced is not transcriptional noise but is likely to be an active participant in establishing or stabilizing these three-dimensional genomic architectures, directly influencing which genes are activated in cancers, such as colorectal carcinoma and hepatocellular carcinoma. This positions certain lncRNAs as master switches for oncogenic transcriptional programs operating at the level of nuclear organization. A powerful example of direct epigenetic control is provided by lncRNA ecCEBP α in acute myeloid leukemia. Functionally, ecCEBP α acts as a physical shield, sequestering DNMT1 from the downstream CEBP α promoter to suppress methylation in cis. Our previous studies have indicated that ecCEBP α can also form RNA-DNA triple helices in trans. These interactions correlate with protection from DNA hypermethylation in patient samples, with binding sites enriched in the promoters of leukemia-associated factors such as MLF2. This suggests a paradigm in which a single lncRNA serves as a direct epigenetic regulator of DNA methylation states both locally and at distant genomic loci via sequence-specific nucleic acid hybridization. Perhaps the most elegant examples come from lncRNAs that regulate factors that shape chromatin. LncRNA CHASERR is not a passive bystander but a precise molecular scaffold, affecting multiple genes and molecular processes in various cell types. 13 – 15 It binds directly to the promoter of the remote NFKBIB gene and recruits the histone methyltransferase EZH2. 16 This leads to the deposition of repressive H3K27me3 marks, silencing an inhibitor of the NF-kB pathway, thereby driving the progression of colorectal cancer. CHASERR itself is localized adjacent to and exerts feedback control over CHD2, a chromodomain helicase DNA-binding protein that is essential for nucleosome remodeling. This places lncRNAs upstream in the regulatory hierarchy, not just as targets of epigenetic machinery, but also as its supervisors. The discovery that haploinsufficiency of CHASERR underlies a severe genetic syndrome, reportedly the first of its kind directly attributable to an lncRNA, is a logical and landmark confirmation of its essential role in human development and genomic integrity. 17 This is not a story of titration or competition, but a story of targeted epigenetic reprogramming. Similarly, MAPKAPK5-AS1 in colorectal cancer functions as a molecular tether that directly binds to and recruits the polycomb repressive complex 2 (PRC2) subunit EZH2 to the promoter of the critical cell cycle inhibitor p21. 18 This recruitment facilitates the deposition of the repressive H3K27me3 histone mark, leading to the transcriptional silencing of p21 and promotion of unchecked cellular proliferation. This mechanism exemplifies a ring and powerful motif in lncRNA biology; they serve as sequence-specific guides or scaffolds, conferring precise genomic targeting to broadly acting chromatin-modifying complexes that would otherwise lack such intrinsic locus specificity. Through this guiding function, lncRNAs such as MAPKAPK5-AS1 translate the general epigenetic machinery into highly specific and often pathological gene expression programs. Another canonical example is X-chromosome inactivation, where JPX evicts the insulator protein CTCF from the Xist promoter, enabling Xist lncRNA to coat the chromosome and recruit repressive complexes to establish stable, heritable silencing. 19 , 20 This is a lncRNA-driven, large-scale epigenetic fate determination. Recent work showing that JPX influences CTCF binding genome-wide suggests that this role in organizing the 3D genome is not an exception, but a potential rule. The consequences of a narrow focus: Diagnostic and therapeutic blind spots The field’s emphasis on cytoplasmic miRNA interactions, reflected in the 3:1 publication ratio has tangible and negative consequences for translational science. By primarily identifying lncRNAs that function as sponges, we overlook the most potent and specific disease drivers and biomarkers. However, the diagnostic potential of lncRNAs is unknown. The expression of epigenetic organizer lncRNAs, such as MAPKAPK5-AS1 and AC005592.2, shows a tight, stage-specific correlation with patient survival in various cancers. Their nuclear regulatory roles may render them more specific markers of malignant transcriptional states than lncRNAs that are involved in broader cytoplasmic regulatory networks. However, biomarker discovery pipelines often prioritize lncRNA-miRNA networks, potentially missing sharper signals. The therapeutic implications are even more significant. Systemic inhibition of ubiquitous epigenetic enzymes, such as EZH2 and DNMT1, causes substantial toxicity, limiting their clinical utility. However, a tumor-specific lncRNA that recruits EZH2 or DNMT1 to a particular oncogenic promoter is an ideal target for precision medicine. Disrupting this single lncRNA-protein interaction could nullify a pathogenic epigenetic event at sources, with minimal off-target effects. Our continued underinvestment in technologies to target nuclear lncRNA complexe—in favor of strategies aimed at cytoplasmic sponge—is a direct consequence of the imbalanced research agenda. The tools to inhibit protein-coding mRNA translation are mature; the tools to disrupt lncRNA-mediated chromatin scaffolding are in their infancy, not due to impossibility, but due to a lack of a prioritized will. A call for conceptual rebalancing Therefore, a paradigm shift is required. This does not mean discarding the well-established concept of lncRNA-miRNA interactions, which clearly explains many important biological phenomena. Instead, it requires that we consciously and deliberately elevate the epigenetic paradigm to a position of equal, if not greater, prominence in our hypotheses, methodologies, and reviews. The publication gap must be closed not by reducing fruitful research on sponging but by actively expanding rigorous exploration of nuclear mechanisms. In practical terms, this means that functional investigation of novel lncRNAs must begin with rigorous detection of their subcellular localization. Nuclear enrichment should immediately trigger a prioritized investigation into maturation associations, histone modification changes, and transcription factor interactions rather than an automatic default in miRNA pulldown assays. Computational and database resources should develop robust classification schemas that highlight “chromatin scaffold,” “transcriptional enhancer,” or “nuclear organizer” as primary functional categories, moving beyond gene ontology terms centered on post-transcriptional regulation. Most importantly, in narrative syntheses, such as review articles and grant proposals, the epigenetic functions of lncRNAs must be framed not as a curious subset but as a fundamental mechanistic pillar. Conclusion Collective evidence is overwhelming. From CHASERR recruiting histone modifiers to specific genes to JPX reshaping CTCF-mediated genome architecture, lncRNAs are repeatedly revealed as central conductors of the epigenetic orchestra. Their ability to provide dynamic, condition-specific, and exquisitely precise targeting of generic chromatin complexes is a function that proteins alone cannot replicate. To remain fixated on the concept of cytoplasmic sponging, as the stark publication disparity suggests, we are to admire the decorative facade of a building while ignoring its structural blueprint. By fully integrating their roles as epigenetic architects into the core narrative of lncRNA biology, we will achieve a better understanding of cellular regulation and unlock a powerful new frontier for targeted disease intervention. The future of the field lies not only in the cytoplasm, but also in the nucleus. Data availability No data are associated with this article. References 1. Hon C-C, Ramilowski JA, Harsh-Barger J, et al. : An atlas of human long non-coding rnas with accurate 5 ends. Nature. 2017; 543 (7644): 199–204. PubMed Abstract | Publisher Full Text 2. Alam T, Medvedeva YA, Jia H, et al. : Promoter analysis reveals globally differential regulation of human long non-coding rna and protein-coding genes. PloS one. 2014; 9 (10): e109443. PubMed Abstract | Publisher Full Text 3. Cabili MN, Trapnell C, Goff L, et al. : Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. September 2011; 25 (18): 1915–1927. PubMed Abstract | Publisher Full Text 4. Quinn JJ, Zhang QC, Georgiev P, et al. : Rapid evolutionary turnover underlies conserved lncRNA- genome interactions. Genes Dev. January 2016; 30 (2): 191–207. PubMed Abstract | Publisher Full Text 5. Ramilowski JA, Yip CW, Agrawal S, et al. : Functional annotation of human long noncoding rnas via molecular phenotyping. Genome Res. 2020; 30 (7): 1060–1072. PubMed Abstract | Publisher Full Text 6. Mazurov E, Sizykh A, Medvedeva YA: Himorna: a comprehensive database of human lncrnas involved in genome-wide epigenetic regulation. Non-coding RNA. 2022; 8 (1): 18. 7. Ilnitskiy IS, Ryabykh GK, Marakulina DA, et al. : Himorna and rna-chrom integration: Chromatin-associated lncrnas in genome-wide epigenetic regulation. bioRxiv. 2024; 2024–05. 8. Cai S, Zhou Y, Pan Y, et al. : Long non-coding RNA A1BG- AS1 promotes tumorigenesis in breast cancer by sponging microRNA-485-5p and consequently increasing expression of FLOT1 expression. Hum. Cell. 2021; 34 (5): 1517–1531. PubMed Abstract | Publisher Full Text 9. Zhao Q, Ke W, Li N, et al. : Identification of potentially relevant genes for myocar- dial infarction using RNA sequencing data analysis. Exp. Ther. Med. November 2017. Publisher Full Text 10. Antonov IV, Mazurov E, Borodovsky M, et al. : Prediction of lncrnas and their interactions with nucleic acids: benchmarking bioinformatics tools. Brief. Bioinform. 2019; 20 (2): 551–564. PubMed Abstract | Publisher Full Text 11. Bonetti A, Agostini F, Suzuki AM, et al. : Radicl-seq identifies general and cell type– specific principles of genome-wide RNA-chromatin interactions. Nat. Commun. 2020; 11 (1): 1018. PubMed Abstract | Publisher Full Text 12. Yan L, Chen H, Tang L, et al. : Super-enhancer-associated long noncoding RNA AC005592.2 promotes tumor progression by regulating OLFM4 in colorectal cancer. BMC Cancer. February 2021; 21 (1): 187. PubMed Abstract | Publisher Full Text 13. Rom A, Melamed L, Gil N, et al. : Regulation of CHD2 expression by the chaserr long noncoding RNA gene is essential for viability. Nat. Commun. November 2019; 10 (1): 5092. PubMed Abstract | Publisher Full Text 14. Antonov I, Medvedeva Y: Direct interactions with nascent transcripts is potentially a common targeting mechanism of long non-coding rnas. Genes. 2020; 11 (12): 1483. Publisher Full Text 15. Budkina A, Zubritskiy A, Marakulina D, et al. : Chaserr-chd2 dynamics in t cell quiescence and its modulation by cyclosporine. Frontiers in Immunology. 2025; 16 : 1652359. Publisher Full Text 16. Liu J, Zhan Y, Wang J, et al. : Long noncoding RNA LINC01578 drives colon cancer metastasis through a positive feedback loop with the NF- κ B/YY1 axis. Mol. Oncol. December 2020; 14 (12): 3211–3233. PubMed Abstract | Publisher Full Text 17. Ganesh VS, Riquin K, Chatron N, et al. : Neurodevelopmental disorder caused by deletion of CHASERR, a lncRNA gene. N. Engl. J. Med. October 2024; 391 (16): 1511–1518. PubMed Abstract | Publisher Full Text 18. Ji H, Hui B, Wang J, et al. : Long noncoding RNA MAPKAPK5- AS1 promotes colorectal cancer proliferation by partly silencing p21 expression. Cancer Sci. January 2019; 110 (1): 72–85. PubMed Abstract | Publisher Full Text 19. Sun S, Del Rosario BC, Szanto A, et al. : Jpx RNA activates xist by evicting CTCF. Cell. June 2013; 153 (7): 1537–1551. PubMed Abstract | Publisher Full Text 20. Richard JLC, Ogawa Y: Understanding the complex circuitry of lncRNAs at the x-inactivation center and its implications in disease conditions. Current Topics in Microbiology and Immunology. Cham: Springer International Publishing; 2015; pages 1–27. Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 27 Jan 2026 ADD YOUR COMMENT Comment Author details Author details 1 Skryabin Institute of Bioengineering, Research Centre of Biotechnology, Mosocw, 117312, Russian Federation Anatoliy V Zubritskiy Roles: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing Yulia A. Medvedeva Roles: Conceptualization, Funding Acquisition, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information This work was partially supported by RSF grant number 23-14-00371 to Y.A.M. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (1) version 1 Published: 27 Jan 2026, 15:120 https://doi.org/10.12688/f1000research.175368.1 Copyright © 2026 Zubritskiy AV and Medvedeva YA. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Zubritskiy AV and Medvedeva YA. From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :120 ( https://doi.org/10.12688/f1000research.175368.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 27 Jan 2026 Views 0 Cite How to cite this report: Montaño-Samaniego M. Reviewer Report For: From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :120 ( https://doi.org/10.5256/f1000research.193347.r458546 ) The direct URL for this report is: https://f1000research.com/articles/15-120/v1#referee-response-458546 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 11 Mar 2026 Mariela Montaño-Samaniego , Instituto Politecnico Nacional, Mexico City, Mexico City, Mexico Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.193347.r458546 This opinion paper argues that studies on long non-coding RNAs (lncRNAs) have been excessively influenced by the concept of cytoplasmic miRNA sponging, which has overshadowed their essential functions within the nucleus. The authors suggest a conceptual change in perceiving lncRNAs ... Continue reading READ ALL This opinion paper argues that studies on long non-coding RNAs (lncRNAs) have been excessively influenced by the concept of cytoplasmic miRNA sponging, which has overshadowed their essential functions within the nucleus. The authors suggest a conceptual change in perceiving lncRNAs as essential architects of the epigenetic environment that direct chromatin-modifying complexes and control genome structure. Examples like SPRY4-AS1, ecCEBPα, CHASERR, and MAPKAPK5-AS1 demonstrate the ability of lncRNAs to influence DNA methylation, histone modifications, and transcriptional regulation. The authors argue that focusing mainly on cytoplasmic processes leads to gaps in diagnosis and treatment. They advocate for increased focus on nuclear lncRNA roles to enhance biomarker identification and create more targeted epigenetic treatments. The central thesis of this opinion paper is stimulating, timely and significant. However, there are several conceptual and logical inconsistencies that weaken the argument; in multiple instances, claims are presented with greater certainty than warranted by current evidence, these should be addressed to strengthen the manuscript: Overstating the “miRNA sponge dominance” narrative The article argues that the field is disproportionately focused on miRNA sponging, citing publication counts (“lncRNA and miRNA” vs “lncRNA and epigenetics”, 23,000 vs 6,500 hits, respectively). However: PubMed keyword counts are not a reliable proxy for dominance. “lncRNA and miRNA” includes any co-mention (regulatory cascades, indirect effects, co-expression studies). “lncRNA and epigenetics” is a constrictive keyword set that excludes numeorus chromatin-related studies not directly identified as “epigenetics.” Significant lncRNAs with nuclear function (e.g., XIST, HOTAIR, ANRIL, NEAT1) have been pivotal in the field for over a decade. The framing suggests that nuclear mechanisms are overlooked, which is not entirely correct . Several nuclear lncRNAs have been central to the field for years. Overgeneralization: “Majority of lncRNAs interact with chromatin” The claim that “the majority of lncRNAs interact with chromatin” is too strong. However: Many lncRNAs are cytoplasmic or have dual localization. Many nuclear lncRNAs show weak or indirect chromatin association. Global RNA–chromatin mapping studies show widespread proximity, but functional relevance is often unclear. Physical chromatin association does not necessarily equate to functional epigenetic regulation. inconsistency: Physical chromatin association ≠ functional chromatin regulation. Overstatement of “Scaffold” Functions The manuscript repeatedly describes lncRNAs as “primary architects,” “master switches,” and locus-specific guides of chromatin-modifying complexes. This language exceeds the strength of evidence in most cases. While this model is compelling, several aspects remain debated. Presenting RNA-guided chromatin targeting as broadly established rather than still under investigation may weaken the scientific rigor of the argument. Internal Logical Tensions The article states: “The diagnostic potential of lncRNAs is unknown.” Yet immediately claims: Stage-specific survival correlations Biomarker promise This is contradictory. A more precise way to express this would be: "The diagnostic potential is promising but not adequately validated in clinical settings". Translational claims and therapeutic optimism The manuscript suggests that targeting tumor-specific lncRNAs would produce minimal off-target effects. This is optimistic because: Many lncRNAs are low abundance. Nuclear targeting delivery remains difficult. Many lncRNAs act in cis; deleting them may disrupt enhancer DNA rather than RNA function. The therapeutic section would benefit from a more realistic appraisal of delivery and specificity barriers. Final recommendation The manuscript raises an important and worthwhile conceptual point: nuclear and epigenetic functions of lncRNAs deserve sustained and rigorous attention. However, the current version presents the argument with excessive certainty. I recommend major revision , with emphasis on: Avoid overgeneralization about field imbalance. Clarify distinctions between chromatin association and functional epigenetic remodeling. Moderate translational optimism. Removal of overstatements Careful distinction between evidence and inference Use up-to-date and relevant literature to justify the certainty expressed, or to more accurately represent the current state of research. With these revisions, the article could make a valuable contribution to the field without sacrificing scientific balance. Is the topic of the opinion article discussed accurately in the context of the current literature? Partly Are all factual statements correct and adequately supported by citations? Partly Are arguments sufficiently supported by evidence from the published literature? Partly Are the conclusions drawn balanced and justified on the basis of the presented arguments? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Biomedicine and Biotechnology applied to the treatment of diseases through the use of microRNAs. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Montaño-Samaniego M. Reviewer Report For: From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :120 ( https://doi.org/10.5256/f1000research.193347.r458546 ) The direct URL for this report is: https://f1000research.com/articles/15-120/v1#referee-response-458546 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Salazar LA. Reviewer Report For: From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :120 ( https://doi.org/10.5256/f1000research.193347.r458547 ) The direct URL for this report is: https://f1000research.com/articles/15-120/v1#referee-response-458547 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 24 Feb 2026 Luis A. Salazar , Universidad Nacional Mayor de San Marcos, Lima District, Lima Region, Peru Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.193347.r458547 This manuscript presents an opinion-based perspective on the role of long non-coding RNAs (lncRNAs), arguing for a conceptual shift from the widely studied miRNA sponging paradigm toward a greater emphasis on their function as epigenetic regulators and chromatin scaffolds. The ... Continue reading READ ALL This manuscript presents an opinion-based perspective on the role of long non-coding RNAs (lncRNAs), arguing for a conceptual shift from the widely studied miRNA sponging paradigm toward a greater emphasis on their function as epigenetic regulators and chromatin scaffolds. The topic is clearly relevant and timely, and the authors raise an interesting and potentially valuable point about how prevailing research trends may shape scientific understanding. The manuscript is also engaging to read and highlights several illustrative examples that support the central argument. However, while the perspective is thought-provoking, there are several aspects that would need to be addressed in order to strengthen the scientific rigor and overall credibility of the article. First, the discussion of the topic is only partially grounded in the current literature. Although key studies are cited, the manuscript does not provide a sufficiently balanced or comprehensive view of recent research. In particular, more up-to-date references (from the last few years) should be incorporated to reflect the current state of the field. Additionally, the argument about a “publication bias” toward cytoplasmic functions is based on a simple comparison of PubMed search results, which is not a robust or widely accepted method for demonstrating conceptual imbalance. A more rigorous bibliometric approach or a clearer explanation of how the comparison was conducted would significantly improve this section. Second, not all factual claims are adequately supported. Some statements are presented in a very definitive manner (e.g., suggesting that nuclear lncRNAs are the most functionally significant or that the evidence is “overwhelming”), but these claims are not backed by systematic evidence. Since this is an opinion article, it is understandable that the authors are advancing a perspective; however, the tone should be adjusted to reflect this. Rephrasing strong claims to more cautious language (e.g., “emerging evidence suggests” or “we propose that”) would make the argument more scientifically appropriate. Third, the arguments are only partially supported by the literature. The manuscript relies on a set of well-chosen examples, but these appear selective and do not necessarily represent the full diversity of lncRNA functions. The absence of counterexamples or alternative interpretations weakens the overall argument. Including a brief discussion acknowledging the continued relevance of cytoplasmic mechanisms, and clarifying that both paradigms can coexist, would provide a more balanced and convincing narrative. Related to this, the conclusions, while consistent with the authors’ line of reasoning, are somewhat stronger than what the presented evidence can fully justify. The manuscript would benefit from moderating its conclusions and clearly distinguishing between established findings and forward-looking hypotheses. There are also some issues with clarity and language that should be addressed. A number of sentences contain minor grammatical errors or awkward phrasing, which may distract readers and reduce the perceived quality of the manuscript. A careful language revision would be helpful. To improve the manuscript and make it scientifically solid, I would recommend the following: * Incorporate more recent and representative literature to better reflect the current state of research. * Provide a more rigorous justification (or remove/simplify) the claim regarding publication bias. * Reframe strong or absolute statements using more cautious, hypothesis-driven language. * Include a more balanced discussion that acknowledges alternative mechanisms and perspectives. * Moderate the conclusions so they align more closely with the level of evidence presented. * Revise the manuscript for clarity, grammar, and overall readability. The manuscript raises an interesting and worthwhile perspective, but it currently reads as more assertive than the supporting evidence allows. With revisions that improve balance, clarity, and evidentiary support, it could make a meaningful contribution to the discussion on lncRNA function. Is the topic of the opinion article discussed accurately in the context of the current literature? Partly Are all factual statements correct and adequately supported by citations? No Are arguments sufficiently supported by evidence from the published literature? Partly Are the conclusions drawn balanced and justified on the basis of the presented arguments? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Applied Technology in Medicine, Biology, and Health Sciences I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Salazar LA. Reviewer Report For: From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :120 ( https://doi.org/10.5256/f1000research.193347.r458547 ) The direct URL for this report is: https://f1000research.com/articles/15-120/v1#referee-response-458547 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 27 Jan 2026 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 27 Jan 26 read read Luis A. Salazar , Universidad Nacional Mayor de San Marcos, Lima District, Peru Mariela Montaño-Samaniego , Instituto Politecnico Nacional, Mexico City, Mexico Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Montaño-Samaniego M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 11 Mar 2026 | for Version 1 Mariela Montaño-Samaniego , Instituto Politecnico Nacional, Mexico City, Mexico City, Mexico 0 Views copyright © 2026 Montaño-Samaniego M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This opinion paper argues that studies on long non-coding RNAs (lncRNAs) have been excessively influenced by the concept of cytoplasmic miRNA sponging, which has overshadowed their essential functions within the nucleus. The authors suggest a conceptual change in perceiving lncRNAs as essential architects of the epigenetic environment that direct chromatin-modifying complexes and control genome structure. Examples like SPRY4-AS1, ecCEBPα, CHASERR, and MAPKAPK5-AS1 demonstrate the ability of lncRNAs to influence DNA methylation, histone modifications, and transcriptional regulation. The authors argue that focusing mainly on cytoplasmic processes leads to gaps in diagnosis and treatment. They advocate for increased focus on nuclear lncRNA roles to enhance biomarker identification and create more targeted epigenetic treatments. The central thesis of this opinion paper is stimulating, timely and significant. However, there are several conceptual and logical inconsistencies that weaken the argument; in multiple instances, claims are presented with greater certainty than warranted by current evidence, these should be addressed to strengthen the manuscript: Overstating the “miRNA sponge dominance” narrative The article argues that the field is disproportionately focused on miRNA sponging, citing publication counts (“lncRNA and miRNA” vs “lncRNA and epigenetics”, 23,000 vs 6,500 hits, respectively). However: PubMed keyword counts are not a reliable proxy for dominance. “lncRNA and miRNA” includes any co-mention (regulatory cascades, indirect effects, co-expression studies). “lncRNA and epigenetics” is a constrictive keyword set that excludes numeorus chromatin-related studies not directly identified as “epigenetics.” Significant lncRNAs with nuclear function (e.g., XIST, HOTAIR, ANRIL, NEAT1) have been pivotal in the field for over a decade. The framing suggests that nuclear mechanisms are overlooked, which is not entirely correct . Several nuclear lncRNAs have been central to the field for years. Overgeneralization: “Majority of lncRNAs interact with chromatin” The claim that “the majority of lncRNAs interact with chromatin” is too strong. However: Many lncRNAs are cytoplasmic or have dual localization. Many nuclear lncRNAs show weak or indirect chromatin association. Global RNA–chromatin mapping studies show widespread proximity, but functional relevance is often unclear. Physical chromatin association does not necessarily equate to functional epigenetic regulation. inconsistency: Physical chromatin association ≠ functional chromatin regulation. Overstatement of “Scaffold” Functions The manuscript repeatedly describes lncRNAs as “primary architects,” “master switches,” and locus-specific guides of chromatin-modifying complexes. This language exceeds the strength of evidence in most cases. While this model is compelling, several aspects remain debated. Presenting RNA-guided chromatin targeting as broadly established rather than still under investigation may weaken the scientific rigor of the argument. Internal Logical Tensions The article states: “The diagnostic potential of lncRNAs is unknown.” Yet immediately claims: Stage-specific survival correlations Biomarker promise This is contradictory. A more precise way to express this would be: "The diagnostic potential is promising but not adequately validated in clinical settings". Translational claims and therapeutic optimism The manuscript suggests that targeting tumor-specific lncRNAs would produce minimal off-target effects. This is optimistic because: Many lncRNAs are low abundance. Nuclear targeting delivery remains difficult. Many lncRNAs act in cis; deleting them may disrupt enhancer DNA rather than RNA function. The therapeutic section would benefit from a more realistic appraisal of delivery and specificity barriers. Final recommendation The manuscript raises an important and worthwhile conceptual point: nuclear and epigenetic functions of lncRNAs deserve sustained and rigorous attention. However, the current version presents the argument with excessive certainty. I recommend major revision , with emphasis on: Avoid overgeneralization about field imbalance. Clarify distinctions between chromatin association and functional epigenetic remodeling. Moderate translational optimism. Removal of overstatements Careful distinction between evidence and inference Use up-to-date and relevant literature to justify the certainty expressed, or to more accurately represent the current state of research. With these revisions, the article could make a valuable contribution to the field without sacrificing scientific balance. Is the topic of the opinion article discussed accurately in the context of the current literature? Partly Are all factual statements correct and adequately supported by citations? Partly Are arguments sufficiently supported by evidence from the published literature? Partly Are the conclusions drawn balanced and justified on the basis of the presented arguments? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Biomedicine and Biotechnology applied to the treatment of diseases through the use of microRNAs. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Montaño-Samaniego M. Peer Review Report For: From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :120 ( https://doi.org/10.5256/f1000research.193347.r458546) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/15-120/v1#referee-response-458546 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Salazar L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 24 Feb 2026 | for Version 1 Luis A. Salazar , Universidad Nacional Mayor de San Marcos, Lima District, Lima Region, Peru 0 Views copyright © 2026 Salazar L. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This manuscript presents an opinion-based perspective on the role of long non-coding RNAs (lncRNAs), arguing for a conceptual shift from the widely studied miRNA sponging paradigm toward a greater emphasis on their function as epigenetic regulators and chromatin scaffolds. The topic is clearly relevant and timely, and the authors raise an interesting and potentially valuable point about how prevailing research trends may shape scientific understanding. The manuscript is also engaging to read and highlights several illustrative examples that support the central argument. However, while the perspective is thought-provoking, there are several aspects that would need to be addressed in order to strengthen the scientific rigor and overall credibility of the article. First, the discussion of the topic is only partially grounded in the current literature. Although key studies are cited, the manuscript does not provide a sufficiently balanced or comprehensive view of recent research. In particular, more up-to-date references (from the last few years) should be incorporated to reflect the current state of the field. Additionally, the argument about a “publication bias” toward cytoplasmic functions is based on a simple comparison of PubMed search results, which is not a robust or widely accepted method for demonstrating conceptual imbalance. A more rigorous bibliometric approach or a clearer explanation of how the comparison was conducted would significantly improve this section. Second, not all factual claims are adequately supported. Some statements are presented in a very definitive manner (e.g., suggesting that nuclear lncRNAs are the most functionally significant or that the evidence is “overwhelming”), but these claims are not backed by systematic evidence. Since this is an opinion article, it is understandable that the authors are advancing a perspective; however, the tone should be adjusted to reflect this. Rephrasing strong claims to more cautious language (e.g., “emerging evidence suggests” or “we propose that”) would make the argument more scientifically appropriate. Third, the arguments are only partially supported by the literature. The manuscript relies on a set of well-chosen examples, but these appear selective and do not necessarily represent the full diversity of lncRNA functions. The absence of counterexamples or alternative interpretations weakens the overall argument. Including a brief discussion acknowledging the continued relevance of cytoplasmic mechanisms, and clarifying that both paradigms can coexist, would provide a more balanced and convincing narrative. Related to this, the conclusions, while consistent with the authors’ line of reasoning, are somewhat stronger than what the presented evidence can fully justify. The manuscript would benefit from moderating its conclusions and clearly distinguishing between established findings and forward-looking hypotheses. There are also some issues with clarity and language that should be addressed. A number of sentences contain minor grammatical errors or awkward phrasing, which may distract readers and reduce the perceived quality of the manuscript. A careful language revision would be helpful. To improve the manuscript and make it scientifically solid, I would recommend the following: * Incorporate more recent and representative literature to better reflect the current state of research. * Provide a more rigorous justification (or remove/simplify) the claim regarding publication bias. * Reframe strong or absolute statements using more cautious, hypothesis-driven language. * Include a more balanced discussion that acknowledges alternative mechanisms and perspectives. * Moderate the conclusions so they align more closely with the level of evidence presented. * Revise the manuscript for clarity, grammar, and overall readability. The manuscript raises an interesting and worthwhile perspective, but it currently reads as more assertive than the supporting evidence allows. With revisions that improve balance, clarity, and evidentiary support, it could make a meaningful contribution to the discussion on lncRNA function. Is the topic of the opinion article discussed accurately in the context of the current literature? Partly Are all factual statements correct and adequately supported by citations? No Are arguments sufficiently supported by evidence from the published literature? Partly Are the conclusions drawn balanced and justified on the basis of the presented arguments? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Applied Technology in Medicine, Biology, and Health Sciences I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Salazar LA. Peer Review Report For: From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic Regulation [version 1; peer review: 2 approved with reservations] . F1000Research 2026, 15 :120 ( https://doi.org/10.5256/f1000research.193347.r458547) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/15-120/v1#referee-response-458547 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Stay Updated Sign up for content alerts and receive a weekly or monthly email with all newly published articles Register with F1000Research Already registered? Sign in Not now, thanks close PLEASE NOTE If you are an AUTHOR of this article, please check that you signed in with the account associated with this article otherwise we cannot automatically identify your role as an author and your comment will be labelled as a “User Comment”. If you are a REVIEWER of this article, please check that you have signed in with the account associated with this article and then go to your account to submit your report, please do not post your review here. If you do not have access to your original account, please contact us . All commenters must hold a formal affiliation as per our Policies . The information that you give us will be displayed next to your comment. User comments must be in English, comprehensible and relevant to the article under discussion. We reserve the right to remove any comments that we consider to be inappropriate, offensive or otherwise in breach of the User Comment Terms and Conditions . Commenters must not use a comment for personal attacks. When criticisms of the article are based on unpublished data, the data should be made available. I accept the User Comment Terms and Conditions Please confirm that you accept the User Comment Terms and Conditions. Affiliation ✕ refresh Please enter your institution. Note: To add your institution or organisation, start typing the name and then select the correct name from the list. Where applicable, the name will appear in both the original language and in English. Do not paste in the name. If the name does not appear in the drop-down list, we will display the information you have entered. ✕ refresh Country/Region * USA UK Canada China France Germany Afghanistan Aland Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory British Virgin Islands Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Cook Islands Costa Rica Cote d'Ivoire Croatia Cuba Cyprus Czech Republic Democratic Republic of the Congo Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Federated States of Micronesia Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and Mcdonald Islands Holy See (Vatican City State) Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Kosovo (Serbia and Montenegro) Kuwait Kyrgyzstan Lao People's Democratic Republic Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macao Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Minor Outlying Islands of the United States Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands Antilles New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island North Korea North Macedonia Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Reunion Romania Russian Federation Rwanda Saint Helena Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Is South Korea South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand The Gambia The Netherlands Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu UK USA Uganda Ukraine United Arab Emirates United States Virgin Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam Wallis and Futuna West Bank and Gaza Strip Western Sahara Yemen Zambia Zimbabwe Please select your country/region. You must enter a comment. Competing Interests Please disclose any competing interests that might be construed to influence your judgment of the article's or peer review report's validity or importance. Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Please state your competing interests The comment has been saved. An error has occurred. Please try again. Cancel Post var lTitle = "From Sponge to Scaffold: Re-centering lncRNAs...".replace("'", ''); var linkedInUrl = "http://www.linkedin.com/shareArticle?url=https://f1000research.com/articles/15-120/v1" + "&title=" + encodeURIComponent(lTitle) + "&summary=" + encodeURIComponent('Read the article by '); var deliciousUrl = "https://del.icio.us/post?url=https://f1000research.com/articles/15-120/v1&title=" + encodeURIComponent(lTitle); var redditUrl = "http://reddit.com/submit?url=https://f1000research.com/articles/15-120/v1" + "&title=" + encodeURIComponent(lTitle); linkedInUrl += encodeURIComponent('Zubritskiy AV and Medvedeva YA'); var offsetTop = /chrome/i.test( navigator.userAgent ) ? 4 : -10; var addthis_config = { ui_offset_top: offsetTop, services_compact : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_expanded : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_custom : [ { name: "LinkedIn", url: linkedInUrl, icon:"/img/icon/at_linkedin.svg" }, { name: "Mendeley", url: "http://www.mendeley.com/import/?url=https://f1000research.com/articles/15-120/v1/mendeley", icon:"/img/icon/at_mendeley.svg" }, { name: "Reddit", url: redditUrl, icon:"/img/icon/at_reddit.svg" }, ] }; var addthis_share = { url: "https://f1000research.com/articles/15-120", templates : { twitter : "From Sponge to Scaffold: Re-centering lncRNAs in Epi- genetic.... Zubritskiy AV and Medvedeva YA, published by " + "@F1000Research" + ", https://f1000research.com/articles/15-120/v1" } }; if (typeof(addthis) != "undefined"){ addthis.addEventListener('addthis.ready', checkCount); addthis.addEventListener('addthis.menu.share', checkCount); } $(".f1r-shares-twitter").attr("href", "https://twitter.com/intent/tweet?text=" + addthis_share.templates.twitter); $(".f1r-shares-facebook").attr("href", "https://www.facebook.com/sharer/sharer.php?u=" + addthis_share.url); $(".f1r-shares-linkedin").attr("href", addthis_config.services_custom[0].url); $(".f1r-shares-reddit").attr("href", addthis_config.services_custom[2].url); $(".f1r-shares-mendelay").attr("href", addthis_config.services_custom[1].url); function checkCount(){ setTimeout(function(){ $(".addthis_button_expanded").each(function(){ var count = $(this).text(); if (count !== "" && count != "0") $(this).removeClass("is-hidden"); else $(this).addClass("is-hidden"); }); }, 1000); } close How to cite this report {{reportCitation}} Cancel Copy Citation Details $(function(){R.ui.buttonDropdowns('.dropdown-for-downloads');}); $(function(){R.ui.toolbarDropdowns('.toolbar-dropdown-for-downloads');}); $.get("/articles/acj/175368/193347") new F1000.Clipboard(); new F1000.ThesaurusTermsDisplay("articles", "article", "193347"); $(document).ready(function() { $( "#frame1" ).on('load', function() { var mydiv = $(this).contents().find("div"); var h = mydiv.height(); console.log(h) }); var tooltipLivingFigure = jQuery(".interactive-living-figure-label .icon-more-info"), titleLivingFigure = tooltipLivingFigure.attr("title"); tooltipLivingFigure.simpletip({ fixed: true, position: ["-115", "30"], baseClass: 'small-tooltip', content:titleLivingFigure + " " }); tooltipLivingFigure.removeAttr("title"); $("body").on("click", ".cite-living-figure", function(e) { e.preventDefault(); var ref = $(this).attr("data-ref"); $(this).closest(".living-figure-list-container").find("#" + ref).fadeIn(200); }); $("body").on("click", ".close-cite-living-figure", function(e) { e.preventDefault(); $(this).closest(".popup-window-wrapper").fadeOut(200); }); $(document).on("mouseup", function(e) { var metricsContainer = $(".article-metrics-popover-wrapper"); if (!metricsContainer.is(e.target) && metricsContainer.has(e.target).length === 0) { $(".article-metrics-close-button").click(); } }); var articleId = $('#articleId').val(); if($("#main-article-count-box").attachArticleMetrics) { $("#main-article-count-box").attachArticleMetrics(articleId, { articleMetricsView: true }); } }); var figshareWidget = $(".new_figshare_widget"); if (figshareWidget.length > 0) { window.figshare.load("f1000", function(Widget) { // Select a tag/tags defined in your page. In this tag we will place the widget. _.map(figshareWidget, function(el){ var widget = new Widget({ articleId: $(el).attr("figshare_articleId") //height:300 // this is the height of the viewer part. [Default: 550] }); widget.initialize(); // initialize the widget widget.mount(el); // mount it in a tag that's on your page // this will save the widget on the global scope for later use from // your JS scripts. This line is optional. //window.widget = widget; }); }); } close Error Close Add Reset F1000.MICROSERVICES.AFFILIATION = ''; $(document).ready(function () { $('.js-affiliations-form').each((index, form) => { new AffiliationForm({ formId: form.id, institutionErrorSelector: '.comment-enter-institution', departmentErrorSelector: '.comment-enter-department', placeSelector: '.js-add-comment-place', stateSelector: '.js-add-comment-state', zipCodeSelector: '.js-add-comment-zipcode', countrySelector: '.js-add-comment-country', countryErrorSelector: '.comment-enter-country', }); }); }); $(document).ready(function () { var reportIds = { "456006": 0, "456004": 0, "456005": 0, "456002": 0, "456003": 0, "456000": 0, "456001": 0, "458542": 0, "458543": 0, "458541": 0, "458550": 0, "458548": 0, "458549": 0, "458546": 4, "458547": 7, "458544": 0, "458545": 0, "455998": 0, "455999": 0, "455997": 0, }; $(".referee-response-container,.js-referee-report").each(function(index, el) { var reportId = $(el).attr("data-reportid"), reportCount = reportIds[reportId] || 0; $(el).find(".comments-count-container,.js-referee-report-views").html(reportCount); }); var uuidInput = $("#article_uuid"), oldUUId = uuidInput.val(), newUUId = "16de4ef8-06b0-4ec8-b609-b727fbffb914"; uuidInput.val(newUUId); $("a[href*='article_uuid=']").each(function(index, el) { var newHref = $(el).attr("href").replace(oldUUId, newUUId); $(el).attr("href", newHref); }); }); An innovative open access publishing platform offering rapid publication and open peer review, whilst supporting data deposition and sharing. Browse Gateways Collections How it Works Contact For Developers Cookie Notice Privacy Notice RSS Submit Your Research Follow us © 2012-2026 F1000 Research Ltd. ISSN 2046-1402 | Legal | Partner of Research4Life • CrossRef • ORCID • FAIRSharing R.templateTests.simpleTemplate = R.template(' $text $text $text $text $text '); R.templateTests.runTests(); var F1000platform = new F1000.Platform({ name: "f1000research", displayName: "F1000Research", hostName: "f1000research.com", id: "1", editorialEmail: "[email protected]", infoEmail: "[email protected]", usePmcStats: true }); $(function(){R.ui.dropdowns('.dropdown-for-authors, .dropdown-for-about, .dropdown-for-myresearch');}); // $(function(){R.ui.dropdowns('.dropdown-for-referees');}); $(document).ready(function () { if ($(".cookie-warning").is(":visible")) { $(".sticky").css("margin-bottom", "35px"); $(".devices").addClass("devices-and-cookie-warning"); } $(".cookie-warning .close-button").click(function (e) { $(".devices").removeClass("devices-and-cookie-warning"); $(".sticky").css("margin-bottom", "0"); }); $("#tweeter-feed .tweet-message").each(function (i, message) { var self = $(message); self.html(linkify(self.html())); }); $(".partner").on("mouseenter mouseleave", function() { $(this).find(".gray-scale, .colour").toggleClass("is-hidden"); }); }); Sign In Remember me Forgotten your password? Sign In Cancel Email or password not correct. Please try again Please wait... $(function(){ // Note: All the setup needs to run against a name attribute and *not* the id due the clonish // nature of facebox... $("a[id=googleSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("GOOGLE"); $("form[id=oAuthForm]").submit(); }); $("a[id=facebookSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("FACEBOOK"); $("form[id=oAuthForm]").submit(); }); $("a[id=orcidSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("ORCID"); $("form[id=oAuthForm]").submit(); }); }); If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here . If you still need help with your Google account password, please click here . You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here . If you still need help with your Facebook account password, please click here . Code not correct, please try again Reset password Cancel Email us for further assistance. Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait... Register $(document).ready(function () { signIn.createSignInAsRow($("#sign-in-form-gfb-popup")); $(".target-field").each(function () { var uris = $(this).val().split("/"); if (uris.pop() === "login") { $(this).val(uris.toString().replace(",","/")); } }); });