A proliferation associated tRNA regulatory nexus on human chromosome 6 plays a central role in cell state-dependent gene expression

A proliferation associated tRNA regulatory nexus on human chromosome 6 plays a central role in cell state-dependent gene expression | 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 proliferation associated tRNA regulatory nexus on human chromosome 6 plays a central role in cell state-dependent gene expression Martin Bushell, Holly Hall, Britt van Abeelen, Joseph Waldron, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7232343/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 Redundancy in the genetic code provides robustness against mutations and errors in translation. It also allows cells to encode additional information within a coding sequence alongside the polypeptide chain itself. Here, we show that genes expressed in different cellular states employ distinct codon usage patterns linked to post-transcriptional regulation of protein expression. During proliferation, gene expression programmes favour codons ending in A or T, while in quiescence, genes are enriched for G or C ending codons. In parallel, the tRNA pool broadly shifts to match the differing codon demands in each state. Further, the majority of tRNA genes up regulated during proliferation are confined to a small, distinct locus on human chromosome 6. Together these findings reveal a striking and previously unreported regulatory programme that exploits redundancy in the genetic code to impose an additional layer of gene expression control, driven by a proliferation-associated tRNA regulatory nexus on chromosome 6. Biological sciences/Genetics/Gene regulation Biological sciences/Cell biology/Mechanisms of disease Biological sciences/Molecular biology/Translation/tRNAs Full Text Additional Declarations There is NO Competing Interest. Supplementary Files 250725CodonPapersupplementaltable.csv Supplemental Table S1 250725CodonPapersupplementalfigures.pdf Supplemental Figures 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. 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. 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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-7232343","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":516434547,"identity":"e412c57a-bb72-4ba0-9f60-0478ab08ba33","order_by":0,"name":"Martin 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