{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:39:25Z","timestamp":1792201165100,"version":"4.4.0"},"reference-count":51,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"16","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,4,18]]},"abstract":"<jats:p>\n            YTH domain\u2013containing family protein 1 (YTHDF1), a reader of N6-methyladenosine (m\n            <jats:sup>6<\/jats:sup>\n            A), has been implicated in regulating RNA metabolism in the cytosol. Here, we report a role of YTHDF1 within the nucleus in response to genotoxic stress. Upon radiation, YTHDF1 is phosphorylated at serine-182 in an ataxia telangiectasia and Rad3-related\u2013dependent manner. This phosphorylation inhibits exportin 1\u2013mediated nuclear export of YTHDF1, resulting in its accumulation within the nucleus. Nuclear YTHDF1 enhances the binding capacity of serine- and arginine-rich splicing factor 2 to a group of m\n            <jats:sup>6<\/jats:sup>\n            A-modified exons, leading to increased exon inclusion. Specifically, YTHDF1 promotes splicing and expression of DNA repair genes, such as\n            <jats:italic>BRCA1<\/jats:italic>\n            and\n            <jats:italic>TP53BP1<\/jats:italic>\n            , thereby mitigating excessive DNA damage. Depletion of YTHDF1 sensitizes cancer cells to radiation treatment. Together, our study reveals a crucial role of YTHDF1 in m\n            <jats:sup>6<\/jats:sup>\n            A-mediated messenger RNA splicing in the DNA damage response, proposing it as a potential target for radiation therapy.\n          <\/jats:p>","DOI":"10.1126\/sciadv.ado7660","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T17:58:56Z","timestamp":1744826336000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Nuclear accumulation of YTHDF1 regulates mRNA splicing in the DNA damage response"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7000-1808","authenticated-orcid":true,"given":"Jingyu","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory of Sir Run Run Shaw Hospital, and School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9954-6550","authenticated-orcid":true,"given":"Yunyi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory of Sir Run Run Shaw Hospital, and School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9834-7242","authenticated-orcid":true,"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory of Sir Run Run Shaw Hospital, and School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5504-345X","authenticated-orcid":true,"given":"Sujun","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory of Sir Run Run Shaw Hospital, and School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9423-1173","authenticated-orcid":true,"given":"Saisai","family":"Wei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8358-6320","authenticated-orcid":true,"given":"Xiangwei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory of Sir Run Run Shaw Hospital, and School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.09.003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.05.015"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10760"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0114-z"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.10.040"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-022-00535-5"},{"key":"e_1_3_2_8_2","first-page":"1233","article-title":"Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N\n                  6-adenosine)-methyltransferase","volume":"3","author":"Bokar J. 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