{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T07:11:14Z","timestamp":1792221074857,"version":"4.4.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFF1000902, 2021YFD1200903"],"award-info":[{"award-number":["2023YFF1000902, 2021YFD1200903"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Staphylococcus aureus<\/jats:italic> (<jats:italic>S. aureus<\/jats:italic>)-induced bovine mastitis is a major challenge for dairy production, causing significant economic losses. The regulatory mechanisms underlying host cell apoptosis and inflammation during <jats:italic>S. aureus<\/jats:italic> infection remain unclear. Therefore, this study investigates the role of N6-methyladenosine (m<jats:sup>6<\/jats:sup>A) modification and its reader protein YTHDF2 in regulating mRNA stability, apoptosis, and inflammation in bovine mammary epithelial cells (Mac-T cells) under <jats:italic>S. aureus<\/jats:italic> challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MeRIP-seq, RIP-seq, and RT-qPCR were used to analyze m<jats:sup>6<\/jats:sup>A-modified <jats:italic>IER3<\/jats:italic> mRNA and its interaction with YTHDF2. Apoptosis, necrosis, and mitochondrial function were assessed using YO-PRO-1\/PI staining and JC-1 assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>S. aureus<\/jats:italic> infection significantly downregulated <jats:italic>YTHDF2<\/jats:italic> expression in Mac-T cells, leading to destabilization of m<jats:sup>6<\/jats:sup>A-modified <jats:italic>IER3<\/jats:italic> mRNA. This resulted in increased reactive oxygen species (ROS) levels, mitochondrial dysfunction, and cell apoptosis. Overexpression of <jats:italic>YTHDF2<\/jats:italic> restored mRNA stability, reduced apoptosis, and preserved mitochondrial function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>YTHDF2 regulates m<jats:sup>6<\/jats:sup>A-modified mRNA stability to modulate apoptosis and inflammation during <jats:italic>S. aureus<\/jats:italic> infection. These findings provide new insights into understanding the molecular mechanisms of bovine mastitis and provide genetic markers for breeding mastitis-resistant dairy cows.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1542647","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T05:46:10Z","timestamp":1748583970000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["YTHDF2-mediated m6A modification regulates mRNA stability of Immediate early response gene 3 to modulate cell death in Staphylococcus aureus-induced bovine mastitis"],"prefix":"10.3389","volume":"15","author":[{"given":"Yue","family":"Xing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjun","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s10911-011-9230-4","article-title":"Immunopathology of mastitis: insights into disease recognition and resolution","volume":"16","author":"Aitken","year":"2011","journal-title":"J. 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