ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Bacteria and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1542647
This article is part of the Research TopicHost – Pathogen Interactions: A One Health PerspectiveView all 3 articles
YTHDF2-mediated m 6 A modification regulates mRNA stability of Immediate early response gene 3 to modulate cell death in Staphylococcus aureus-induced bovine mastitis
Provisionally accepted
- 1China Agricultural University, Beijing, China
- 2Westlake University, Hangzhou, Zhejiang, China
- 3Ningxia University, Yinchuan, Ningxia Hui Region, China
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Background: Staphylococcus aureus (S. aureus)-induced bovine mastitis is a major challenge for dairy production, causing significant economic losses. The regulatory mechanisms underlying host cell apoptosis and inflammation during S. aureus infection remain unclear. Therefore, this study investigates the role of N6-methyladenosine (m 6 A) modification and its reader protein YTHDF2 in regulating mRNA stability, apoptosis, and inflammation in bovine mammary epithelial cells (Mac-T cells) under S. aureus challenge. Methods: MeRIP-seq, RIP-seq, and RT-qPCR were used to analyze m 6 A-modified IER3 mRNA and its interaction with YTHDF2. Apoptosis, necrosis, and mitochondrial function were assessed using YO-PRO-1/PI staining and JC-1 assays. Results: S. aureus infection significantly downregulated YTHDF2 expression in Mac-T cells, leading to destabilization of m 6 A-modified IER3 mRNA. This resulted in increased reactive oxygen species (ROS) levels, mitochondrial dysfunction, and cell apoptosis. Overexpression of YTHDF2 restored mRNA stability, reduced apoptosis, and preserved mitochondrial function. Conclusion: YTHDF2 regulates m 6 A-modified mRNA stability to modulate apoptosis and inflammation during S. aureus infection. These findings provide new insights into understanding the molecular mechanisms of bovine mastitis and provide genetic markers for breeding mastitis-resistant dairy cows.
Keywords: Bovine Mastitis, Staphylococcus aureus, YTHDF2, M 6 A modification, Apoptosis and necrosis
Received: 10 Dec 2024; Accepted: 06 May 2025.
Copyright: © 2025 Xing, Mi, Chen, Tao, Zhang, Shi, Wang and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ying Yu, China Agricultural University, Beijing, China
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