{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:11:11Z","timestamp":1791069071372,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Innate immunity is the first line of defense against infections, which functions as a significant role in resisting pathogen invasion. Rapid immune response is initiated by pattern recognition receptors (PRRs) quickly distinguishing \u201cself\u201d and \u201cnon\u2010self.\u201d Upon evolutionarily conserved pathogen\u2010associated molecular pattern (PAMP) is recognized by PRRs, innate immune response against infection is triggered via an orchestration of molecular interaction, cytokines cascades, and immune cells. RIG\u2010I plays a critical role in type I interferon (IFN\u2010I) production by direct recognition of cytoplasmic double\u2010stranded viral RNA. However, the activation mechanism of RIG\u2010I is incompletely understood. In this study, we reported RNA\u2010binding protein ZFP36 as a positive regulator of RIG\u2010I\u2010mediated IFN\u2010I production. ZFP36 is a member of Zinc finger proteins (ZFPs) characterized by the zinc finger (ZnF) motif, which broadly involved gene transcription and signal transduction. However, its role in regulating antiviral innate immune signaling is still unclear. We found that ZFP36 associates with RIG\u2010I and potentiates the FN\u2010\u03b2 production induced by SeV. Mechanistically, ZFP36 promotes K63\u2010linked polyubiquitination of RIG\u2010I, mostly at K154\/K164\/K172, thereby facilitating the activation of RIG\u2010I during infection. While the mutant ZFP36 (C118S\/C162S) failed to increase polyubiquitination of RIG\u2010I and SeV induced FN\u2010\u03b2. Our findings collectively demonstrated that ZFP36 acts as a positive regulator in antiviral innate immunity by targeting RIG\u2010I for K63\u2010linked ubiquitination, thus improving our understanding of the activation mechanism of RIG\u2010I.<\/jats:p>","DOI":"10.1002\/jcp.31088","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T10:50:41Z","timestamp":1691664641000},"page":"2348-2360","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The RNA\u2010binding protein ZFP36 strengthens innate antiviral signaling by targeting RIG\u2010I for K63\u2010linked ubiquitination"],"prefix":"10.1002","volume":"238","author":[{"given":"Xue","family":"Jiang","sequence":"first","affiliation":[{"name":"College of Life Science Jiangxi Normal University Nanchang Jiangxi 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