OMVs-Delivered Vibrio splendidus sRNA063 OrchestratesPDZRN3-Mediated K48-Linked Polyubiquitination of ATG2 toSuppress Autophagy in Echinoderms | 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 OMVs-Delivered Vibrio splendidus sRNA063 OrchestratesPDZRN3-Mediated K48-Linked Polyubiquitination of ATG2 toSuppress Autophagy in Echinoderms Tao wenjun, Li chenghua This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8922027/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 Pathogenic small RNAs (sRNAs) are emerging as cross-kingdom regulators of host immunity, yet the underlying mechanism remains incompletely defined. Here, we identify sRNA063 as a key virulence gene of Vibrio splendidus during the infection of its host, sea cucumber Apostichopus japonicus. sRNA063 is delivered to host coelomocytes via outer membrane vesicles (OMVs) and directly binds the A. japonicus autophagy-related protein 2 (AjATG2), accelerating its degradation through the ubiquitin-proteasome system (UPS) without affecting transcription. Mechanistically, sRNA063 functions as a “molecular scaffold” that recruits the E3 ubiquitin ligase AjPDZRN3, strengthens the AjATG2-AjPDZRN3 binding affinity and suppresses AjPDZRN3 self-ubiquitination. This interaction promotes K48-linked polyubiquitination of AjATG2, thereby impairing autophagy and facilitating intracellular V. splendidus survival. Collectively, these findings uncover a novel cross- kingdom regulation mechanism whereby bacterial sRNAs modulate host protein ubiquitination through scaffolding activity Immunology Apostichopus japonicus AjATG2 AjPDZRN3 Full Text Additional Declarations The authors declare no competing interests. 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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