5′-tRNAGly(GCC) halves generated by IRE1α are linked to ER stress response

5′-tRNAGly(GCC) halves generated by IRE1α are linked to ER stress response | 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 5′-tRNA Gly(GCC) halves generated by IRE1α are linked to ER stress response Ji-Hyun Yeom, Eunkyoung Shin, Yoonjie Ha, Minju Joo, Hanyong Jin, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1464849/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Oct, 2024 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Transfer RNA (tRNA) halves (tRHs) have various biological functions. However, the biogenesis of specific 5′-tRHs under certain conditions remains unknown. Here, we report that inositol-requiring enzyme 1α (IRE1α) cleaves the anticodon stem-loop region of tRNAGly(GCC) to produce 5′-tRHs (5′-tRH-GlyGCC) with highly selective target discrimination upon endoplasmic reticulum (ER) stress. We observed IRE1α expression-dependent 5′-tRH-GlyGCC production in human cancer cells. Levels of 5′-tRH-GlyGCC were positively correlated with the degree of cancer cell proliferation both in vitro and in vivo; this effect required co-expression of two nuclear ribonucleoproteins, HNRNPM and HNRNPH2, which we identified as binding proteins of 5′-tRH-GlyGCC. In addition, 5′-tRH-GlyGCC modulated mRNA isoform biogenesis. Furthermore, under ER stress in vivo, we observed simultaneous induction of IRE1α and 5′-tRH-GlyGCC expression in mouse organs and a distantly related organism, Cryptococcus neoformans. Thus, collectively, our findings indicate an evolutionarily conserved function for IRE1α-generated 5′-tRH-GlyGCC in cellular adaptation upon ER stress. IRE1α alternative splicing tRNAGly(GCC) ER stress HNRNPM HNRNPH2 tRNA halves Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryTable110DB.pdf Cite Share Download PDF Status: Published Journal Publication published 28 Oct, 2024 Read the published version in Nature Communications → 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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