YTHDF2-mediated mA modification regulates mRNA stability of to modulate cell death in induced bovine mastitis.

Front Cell Infect Microbiol

State Key Laboratory of Animal Biotech Breeding, National Engineering Laboratory for Animal Breeding, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, China.

Published: June 2025


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Article Abstract

Background: ()-induced bovine mastitis is a major challenge for dairy production, causing significant economic losses. The regulatory mechanisms underlying host cell apoptosis and inflammation during infection remain unclear. Therefore, this study investigates the role of N6-methyladenosine (mA) modification and its reader protein YTHDF2 in regulating mRNA stability, apoptosis, and inflammation in bovine mammary epithelial cells (Mac-T cells) under challenge.

Methods: MeRIP-seq, RIP-seq, and RT-qPCR were used to analyze mA-modified mRNA and its interaction with YTHDF2. Apoptosis, necrosis, and mitochondrial function were assessed using YO-PRO-1/PI staining and JC-1 assays.

Results: infection significantly downregulated expression in Mac-T cells, leading to destabilization of mA-modified mRNA. This resulted in increased reactive oxygen species (ROS) levels, mitochondrial dysfunction, and cell apoptosis. Overexpression of restored mRNA stability, reduced apoptosis, and preserved mitochondrial function.

Conclusion: YTHDF2 regulates mA-modified mRNA stability to modulate apoptosis and inflammation during infection. These findings provide new insights into understanding the molecular mechanisms of bovine mastitis and provide genetic markers for breeding mastitis-resistant dairy cows.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162568PMC
http://dx.doi.org/10.3389/fcimb.2025.1542647DOI Listing

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