{"paper_id":"459c848a-da26-433d-aef0-c9424914e045","body_text":"piRNAs safeguard splicing and RNA fidelity during heat shock | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (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;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article piRNAs safeguard splicing and RNA fidelity during heat shock Veena Prahlad, Sehee Min, Johnny Cruz-Corchado This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7966420/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Piwi-interacting RNAs (piRNAs) silence transposons and foreign sequences; yet, for poorly understood reasons, they also extensively target endogenous mRNAs. Here, we report a previously unappreciated role for the Caenorhabditis elegans piRNA pathway in RNA quality control: during heat shock, piRNAs generate endogenous antisense RNAs (endo-siRNAs) that associate with RNA Polymerase II and nascent stress-induced RNAs to delay splicing when the spliceosome is compromised, minimizing transcript errors. In the absence of piRNAs, nascent transcripts undergo premature splicing, accumulate errors, and activate nonsense-mediated decay (NMD) to limit the production of aberrant proteins. We propose that by regulating splicing, the piRNA pathway acts alongside NMD as a quality-control system, safeguarding RNA fidelity and proteome integrity with genome defense. Biological sciences/Molecular biology/RNA metabolism/RNA splicing Biological sciences/Molecular biology/Protein folding/Protein aggregation piRNA heat shock hsp splicing nonsense-mediated decay (NMD) endo-siRNAs transcript fidelity RNA quality control protein homeostasis C. elegans Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryTable12GOHigherErrorsPRDE1.csv Supplementary Table 12 SupplementaryTable11pileupErrorRatesperGene.csv Supplementary Table 11 SupplementaryTable3overlapDEG.mRNAwithDEG.22GsRNA.xlsx Supplementary Table 3 SupplementaryTable13HaplotypeCalledVariants.xlsx Supplementary Table 13 SupplementaryTable422GRNAclassesandmRNAs.xlsx Supplementary Table 4 SupplementaryTable7SUPPA.Events.significant.xlsx Supplementary Table 7 SupplementaryTable8GOASWTandPRDE1.csv Supplementary Table 8 SupplementaryTable2sig.sRNA.xlsx Supplementary Table 2 SupplementaryTable1mRNA.xlsx Supplementary Table 1 SupplementaryTable10AlleleProportionsVariantOnly.docx Supplementary Table 10 SupplementaryTable9genelengthsbyquantile.xlsx Supplementary Table 9 SupplementaryTable6dPSIWTandPRDE1.xlsx Supplementary Table 6 SupplementaryTable5GO22GRNAs.csv Supplementary Table 5 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-7966420\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":592316668,\"identity\":\"a71f8d5a-46ad-4362-8465-59490fa2cf9a\",\"order_by\":0,\"name\":\"Veena 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