Exercise promotes skeletal muscle growth in adolescents via modulating Mettl3-mediated m6A methylation of MyoD in muscle satellite cells
Abstract 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 mechanism...
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| Language: | English |
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BMC
2024-12-01
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| Series: | Cellular & Molecular Biology Letters |
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| Online Access: | https://doi.org/10.1186/s11658-024-00670-x |
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| author | Shujing Feng Hao Zhou Xingzuan Lin Siyuan Zhu Huifang Chen Han Zhou Ru Wang Peng Wang Xiexiang Shao Jianhua Wang |
| author_facet | Shujing Feng Hao Zhou Xingzuan Lin Siyuan Zhu Huifang Chen Han Zhou Ru Wang Peng Wang Xiexiang Shao Jianhua Wang |
| author_sort | Shujing Feng |
| collection | DOAJ |
| description | Abstract 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. Mettl3-mediated m6A methylation regulated MyoD mRNA stability at the posttranscriptional level in MuSCs, with a functional site at 234 bp A. Increased expression of MyoD could contribute to myogenesis of adolescent MuSCs. Furthermore, the methyl donor betaine could enhance MyoD expression, contributing to MuSCs activation and skeletal muscle growth in adolescents by boosting m6A methylation levels. Conclusions Exercise promoted skeletal muscle growth in adolescents through facilitating MyoD mRNA stability of MuSCs in a Mettl3-mediated m6A-dependent manner. The methyl donor betaine could be a potential alternative to exercise for promoting adolescent skeletal muscle growth by directly augmenting the global levels of m6A methylation. These findings may provide a theoretical foundation for encouraging daily fitness exercise and ensuring healthy growth in adolescents. |
| format | Article |
| id | doaj-art-b01d53d8083d467b8a8cda92f405f8a0 |
| institution | Kabale University |
| issn | 1689-1392 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj-art-b01d53d8083d467b8a8cda92f405f8a02024-12-08T12:37:28ZengBMCCellular & Molecular Biology Letters1689-13922024-12-0129112310.1186/s11658-024-00670-xExercise promotes skeletal muscle growth in adolescents via modulating Mettl3-mediated m6A methylation of MyoD in muscle satellite cellsShujing Feng0Hao Zhou1Xingzuan Lin2Siyuan Zhu3Huifang Chen4Han Zhou5Ru Wang6Peng Wang7Xiexiang Shao8Jianhua Wang9Xinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineXinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking UniversityDepartment of Hand Surgery, Huashan Hospital, Fudan UniversitySchool of Exercise and Health, Shanghai University of SportXinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineSchool of Exercise and Health, Shanghai University of SportXinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineXinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineXinhua Hospital affiliated to Shanghai Jiao Tong University School of MedicineAbstract 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. Mettl3-mediated m6A methylation regulated MyoD mRNA stability at the posttranscriptional level in MuSCs, with a functional site at 234 bp A. Increased expression of MyoD could contribute to myogenesis of adolescent MuSCs. Furthermore, the methyl donor betaine could enhance MyoD expression, contributing to MuSCs activation and skeletal muscle growth in adolescents by boosting m6A methylation levels. Conclusions Exercise promoted skeletal muscle growth in adolescents through facilitating MyoD mRNA stability of MuSCs in a Mettl3-mediated m6A-dependent manner. The methyl donor betaine could be a potential alternative to exercise for promoting adolescent skeletal muscle growth by directly augmenting the global levels of m6A methylation. These findings may provide a theoretical foundation for encouraging daily fitness exercise and ensuring healthy growth in adolescents.https://doi.org/10.1186/s11658-024-00670-xExerciseAdolescent skeletal muscle growthMuSCsMettl3m6A methylationBetaine |
| spellingShingle | Shujing Feng Hao Zhou Xingzuan Lin Siyuan Zhu Huifang Chen Han Zhou Ru Wang Peng Wang Xiexiang Shao Jianhua Wang Exercise promotes skeletal muscle growth in adolescents via modulating Mettl3-mediated m6A methylation of MyoD in muscle satellite cells Cellular & Molecular Biology Letters Exercise Adolescent skeletal muscle growth MuSCs Mettl3 m6A methylation Betaine |
| title | Exercise promotes skeletal muscle growth in adolescents via modulating Mettl3-mediated m6A methylation of MyoD in muscle satellite cells |
| title_full | Exercise promotes skeletal muscle growth in adolescents via modulating Mettl3-mediated m6A methylation of MyoD in muscle satellite cells |
| title_fullStr | Exercise promotes skeletal muscle growth in adolescents via modulating Mettl3-mediated m6A methylation of MyoD in muscle satellite cells |
| title_full_unstemmed | Exercise promotes skeletal muscle growth in adolescents via modulating Mettl3-mediated m6A methylation of MyoD in muscle satellite cells |
| title_short | Exercise promotes skeletal muscle growth in adolescents via modulating Mettl3-mediated m6A methylation of MyoD in muscle satellite cells |
| title_sort | exercise promotes skeletal muscle growth in adolescents via modulating mettl3 mediated m6a methylation of myod in muscle satellite cells |
| topic | Exercise Adolescent skeletal muscle growth MuSCs Mettl3 m6A methylation Betaine |
| url | https://doi.org/10.1186/s11658-024-00670-x |
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