miR29 imposes quiescence in mature B cells by repressing the SP1/MYC/miR17-92 activation circuit

miR29 imposes quiescence in mature B cells by repressing the SP1/MYC/miR17-92 activation circuit | 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 Research Article miR29 imposes quiescence in mature B cells by repressing the SP1/MYC/miR17-92 activation circuit Ofer Harel, Naythan Dcunha, Eli Benchetrit, Caterina Canetta, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9169386/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 3 You are reading this latest preprint version Abstract Cellular quiescence is a defining feature of mature immune cells, balancing long-term survival with the capacity for rapid activation while preserving tissue homeostasis. Despite its importance, the molecular mechanisms enforcing quiescence remain incompletely understood. In the B lineage, regulation of the PTEN/PI3K signaling axis is critical for the survival of quiescent cells. We previously demonstrated that miR29 replaces miR17-92 in controlling PTEN/PI3K signaling during B-cell maturation. Here, we show that miR29 expression in mature B cells is essential for imposing and maintenance of their quiescence stage. Using a miR29 targeting antagomiR and conditional ablation of miR29 in CD23-expressing B cells, we show that repression of miR29 in mature quiescent B cells enhances PI3K signaling and induces miR17-92 expression. This regulatory switch promotes increased survival and exit from cellular quiescence. Mechanistically, we found that miR29 represses SP1 in quiescent B cells, thereby limiting MYC expression and the downstream induction of miR17-92. Together, our results suggest that miR29 imposes cellular quiescence in mature B cells by repressing the SP1/MYC/miR17-92 activating axis, illustrating how dynamic microRNA networks remodel intracellular programs to control cellular states. Full Text Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 06 Apr, 2026 Editor assigned by journal 23 Mar, 2026 First submitted to journal 22 Mar, 2026 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-9169386","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":617983311,"identity":"93e7cf55-38a2-4df0-9d31-849896849393","order_by":0,"name":"Ofer Harel","email":"","orcid":"","institution":"Technion Israel Institute of Technology","correspondingAuthor":false,"prefix":"","firstName":"Ofer","middleName":"","lastName":"Harel","suffix":""},{"id":617983312,"identity":"40c18c14-f0b3-43cc-b2aa-8cdc72563a67","order_by":1,"name":"Naythan Dcunha","email":"","orcid":"","institution":"Technion Israel Institute of 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