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Upon interacting with RIG-I, MAVS undergoes K63-linked polyubiquitination by the E3 ligase Trim31, and subsequently aggregates to activate downstream signaling effectors. However, the molecular mechanisms that modulate MAVS activation are not yet fully understood. In this study, the mitochondrial solute carrier SLC25A23 was found to attenuate type I IFN antiviral immunity using genome-wide CRISPR\/Cas9 screening. SLC25A23 interacts with Trim31, interfering with its binding of Trim31 to MAVS. Indeed, SLC25A23 downregulation was found to increase K63-linked polyubiquitination and subsequent aggregation of MAVS, which promoted type I IFN production upon RNA virus infection. Consistently, mice with SLC25A23 knockdown were more resistant to RNA virus infection in vivo. These findings establish SLC25A23 as a novel regulator of MAVS posttranslational modifications and of type I antiviral immunity.<\/jats:p>","DOI":"10.4049\/jimmunol.2300187","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T15:55:48Z","timestamp":1694447748000},"page":"1406-1417","source":"Crossref","is-referenced-by-count":3,"title":["Genome-Wide CRISPR\/Cas9 Screening Identifies That Mitochondrial Solute Carrier SLC25A23 Attenuates Type I IFN Antiviral Immunity via Interfering with MAVS Aggregation"],"prefix":"10.1093","volume":"211","author":[{"given":"Hongguang","family":"Zhang","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University , Suzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University , Suzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University , Suzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianxian","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University , Suzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University , Suzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4471-5983","authenticated-orcid":false,"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, The Affiliated Hospital of Qingdao University , Qingdao ,","place":["China"]},{"name":"Department of Genetics and Cell Biology, Basic Medical College, Qingdao University , Qingdao ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University , Suzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4019-2791","authenticated-orcid":false,"given":"Sidong","family":"Xiong","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University , Suzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunsheng","family":"Dong","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University , Suzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,9,11]]},"reference":[{"key":"2025020406160425200_r1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3109\/08830185.2010.529976","article-title":"Pathogen recognition by the innate immune system","volume":"30","author":"Kumar","year":"2011","journal-title":"Int. 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