Exercise promotes skeletal muscle growth in adolescents via modulating Mettl3-mediated m6A methylation of MyoD in muscle satellite cells

作者：Shujing Feng, Hao Zhou, Xingzuan Lin, Siyuan Zhu, Huifang Chen, Han Zhou, Ru Wang, Peng Wang, Xiexiang Shao, Jianhua Wang · 发表于：Cellular & Molecular Biology Letters · 年份：2024 · DOI：10.1186/s11658-024-00670-x · 被引用次数：11 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、Epigenetics and DNA Methylation

BACKGROUND: Exercise exerts positive impacts on skeletal muscle health and homeostasis. Emerging evidence suggests that m6A methylation is involved in various physiological processes. However, the impact of exercise on adolescent skeletal muscle growth and the underlying epigenetic mechanisms remain poorly understood. METHODS: The lower-limb skeletal muscles were harvested from exercise and control groups to compare the skeletal muscle growth in adolescents. mRNA sequencing was conducted to explore the mechanisms underlying enhanced skeletal muscle growth following exercise. The effects and mechanisms of Mettl3-mediated m6A methylation on adolescent skeletal muscle growth were investigated using muscle satellite cell (MuSC)-specific Mettl3 knockout (KO) mice. The potential function of MyoD for skeletal muscle growth in adolescents was explored by phenotypes after overexpression and evaluation of in vivo myogenesis. Additionally, the effects of the methyl donor betaine on adolescent skeletal muscle growth were investigated in vitro and in vivo. RESULTS: Exercise could promote skeletal muscle growth in adolescents. Sequencing data analysis and confirmation assays uncovered that exercise significantly increased Mettl3-mediated m6A methylation and elevated the expression levels of activation marker MyoD in MuSCs. Establishment of MuSC-specific Mettl3 KO mice further demonstrated that Mettl3-mediated m6A methylation in MyoD contributed to skeletal muscle growth during adolescence....