{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["11(16)"],"submitter":["Hou J"],"pubmed_abstract":["YTH domain-containing family protein 1 (YTHDF1), a reader of N6-methyladenosine (m<sup>6</sup>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-dependent manner. This phosphorylation inhibits exportin 1-mediated 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<sup>6</sup>A-modified exons, leading to increased exon inclusion. Specifically, YTHDF1 promotes splicing and expression of DNA repair genes, such as <i>BRCA1</i> and <i>TP53BP1</i>, 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<sup>6</sup>A-mediated messenger RNA splicing in the DNA damage response, proposing it as a potential target for radiation therapy."],"journal":["Science advances"],"pagination":["eado7660"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12002136"],"repository":["biostudies-literature"],"pubmed_title":["Nuclear accumulation of YTHDF1 regulates mRNA splicing in the DNA damage response."],"pmcid":["PMC12002136"],"pubmed_authors":["Hou J","Han B","Wei S","Gao Y","Yan S","Gao X"],"additional_accession":[]},"is_claimable":false,"name":"Nuclear accumulation of YTHDF1 regulates mRNA splicing in the DNA damage response.","description":"YTH domain-containing family protein 1 (YTHDF1), a reader of N6-methyladenosine (m<sup>6</sup>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-dependent manner. This phosphorylation inhibits exportin 1-mediated 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<sup>6</sup>A-modified exons, leading to increased exon inclusion. Specifically, YTHDF1 promotes splicing and expression of DNA repair genes, such as <i>BRCA1</i> and <i>TP53BP1</i>, 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<sup>6</sup>A-mediated messenger RNA splicing in the DNA damage response, proposing it as a potential target for radiation therapy.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Apr","modification":"2025-07-03T03:04:24.676Z","creation":"2025-07-03T03:04:24.676Z"},"accession":"S-EPMC12002136","cross_references":{"pubmed":["40238889"],"doi":["10.1126/sciadv.ado7660"]}}