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Adv."],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    <jats:sup>6<\/jats:sup>\n                    -Methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) is primarily enriched in the last exons and 3\u2032 untranslated regions (3\u2032UTRs) of messenger RNAs (mRNAs) and is associated with T cell homeostasis. Upon T cell activation, global mRNA 3\u2032UTR shortening is facilitated through alternative polyadenylation (APA). However, it is unclear how T cells coordinate these two important posttranscriptional regulatory events to maintain quiescence. Here, we found that the m\n                    <jats:sup>6<\/jats:sup>\n                    A \u201cwriter\u201d METTL3 directly interacts with APA factor NUDT21 and guided poly(A) site selection. Deletion of\n                    <jats:italic toggle=\"yes\">Nudt21<\/jats:italic>\n                    in T cells resulted in simultaneous overactivation and accelerated apoptosis, leading to T cell loss and impaired adaptive immune function. Mechanistically, METTL3 recruits NUDT21 to the proximal poly(A) site of\n                    <jats:italic toggle=\"yes\">Rragd<\/jats:italic>\n                    mRNA, generating long 3\u2032UTR with m\n                    <jats:sup>6<\/jats:sup>\n                    A modifications.\n                    <jats:italic toggle=\"yes\">Nudt21<\/jats:italic>\n                    deficiency causes\n                    <jats:italic toggle=\"yes\">Rragd<\/jats:italic>\n                    3\u2032UTR shortening and increases\n                    <jats:italic toggle=\"yes\">Rragd<\/jats:italic>\n                    expression, leading to overactivation of mammalian target of rapamycin signaling. Our study reveals an m\n                    <jats:sup>6<\/jats:sup>\n                    A-guided poly(A) site selection mechanism and defines in vivo roles of m\n                    <jats:sup>6<\/jats:sup>\n                    A-APA cross-talk in maintaining T cell quiescence.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea4983","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T18:00:56Z","timestamp":1778695256000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["m\n                    <sup>6<\/sup>\n                    A RNA modification guides alternative polyadenylation to maintain T cell quiescence"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3618-2315","authenticated-orcid":true,"given":"Xingli","family":"Zhang","sequence":"first","affiliation":[{"name":"Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."},{"name":"Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China."},{"name":"FuRong Laboratory, Changsha 410078, Hunan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2767-1784","authenticated-orcid":true,"given":"Haixin","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."},{"name":"Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine, Shanghai 200092, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6941-7363","authenticated-orcid":true,"given":"Gaoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3294-6358","authenticated-orcid":true,"given":"Shan","family":"Miao","sequence":"additional","affiliation":[{"name":"Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajuan","family":"Hao","sequence":"additional","affiliation":[{"name":"Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong 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Virology &amp; Immunology, Institute Pasteur of Shanghai, CAS Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0871-7666","authenticated-orcid":true,"given":"Bing","family":"Su","sequence":"additional","affiliation":[{"name":"Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5948-1596","authenticated-orcid":true,"given":"Yuzhang","family":"Wu","sequence":"additional","affiliation":[{"name":"Chongqing International Institute for Immunology, Chongqing 401338, 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