A retroelement-derived mammalian ARC protein exhibits selective RNA recognition and nucleic acid chaperone functions

A retroelement-derived mammalian ARC protein exhibits selective RNA recognition and nucleic acid chaperone functions | 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 A retroelement-derived mammalian ARC protein exhibits selective RNA recognition and nucleic acid chaperone functions Julita Gumna-Mikina, Angelika Andrzejewska-Romanowska, Maciej Antczak, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6767839/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Activity-regulated cytoskeleton-associated protein (ARC) is an RNA-binding protein that also serves as a central hub for neuronal protein-protein interactions. It is essential for intercellular signaling and contributes to synaptic plasticity. ARC includes Gag-like sequences of Ty3/Gypsy retrotransposons and retains the ability to self-assemble into capsid-like structures containing Arc mRNA. Here, we employ an integrative approach to provide the first detailed in vitro analysis of ARC-RNA interactions. Using quantitative binding assays, RNA structure mapping, and RNP footprinting, complemented by extensive computational analyses, we identified Arc mRNA regions specifically and non-specifically bound by ARC, as well as ARC amino acid residues involved in RNA interactions. We show that ARC recognizes RNA sequence and structure. A specific GC-rich motif is common to all bound RNA sequences, and the binding preferentially occurs near highly stable, solvent-exposed helices in the 5' region of Arc mRNA. Surprisingly, the conserved CDS seems more relevant to binding specificity than the 5' UTR. Our predictions suggest that ARC binding to RNA through positively charged regions of matrix and capsid domains exposes an oligomerization motif, enhancing binding cooperativity. We also provide evidence that ARC acts as a nucleic acid chaperone and can locally destabilize Arc mRNA structure. Biological sciences/Neuroscience/Transporters in the nervous system Biological sciences/Structural biology/Molecular modelling Biological sciences/Biochemistry/Proteins/RNA-binding proteins Biological sciences/Biochemistry/RNA Biological sciences/Neuroscience/Molecular neuroscience ARC Arg3.1 RNA-protein interactions RNA structure RNA transport Full Text Additional Declarations The authors declare no competing interests. Supplementary Files GumnaMikinaetal.Supplementarydata1resubmission.pdf Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6767839","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":472717142,"identity":"d494b3d5-14ed-47ce-9de7-4b1c63886ad8","order_by":0,"name":"Julita Gumna-Mikina","email":"","orcid":"https://orcid.org/0000-0002-1045-2823","institution":"Institute of Bioorganic Chemistry, Polish Academy of Sciences","correspondingAuthor":false,"prefix":"","firstName":"Julita","middleName":"","lastName":"Gumna-Mikina","suffix":""},{"id":472717143,"identity":"c8d053c8-23ad-4b8f-a4a3-a7bf3e206443","order_by":1,"name":"Angelika 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