Ythdf2 facilitates precursor miR-378/miR-378-5p maturation to support myogenic differentiation
文献类型： 外文期刊
作者： Deng, Kaiping 1 ; Su, Yalong 1 ; Liu, Zhipeng 1 ; Hu, Silu 3 ; Ren, Caifang 4 ; Wei, Wurilege 2 ; Fan, Yixuan 1 ; Zhang, Yanli 1 ; Wang, Feng 1 ;
作者机构： 1.Nanjing Agr Univ, Sanya Inst, Coll Plant Protect, Nanjing 210095, Peoples R China
2.Nanjing Agr Univ, Jiangsu Livestock Embryo Engn Lab, Nanjing 210095, Peoples R China
3.Sichuan Univ, Frontiers Sci Ctr Dis Related Mol Network, Lab Pulm Immunol & Inflammat, Chengdu 610200, Peoples R China
4.Jiangsu Univ, Sch Med, Dept Pathol, Nanjing 212013, Peoples R China
5.Inner Mongolia Acad Agr & Anim Husb Sci, Hohhot 010000, Inner Mongolia, Peoples R China
关键词： Ythdf2; pre-miRNA processing; miR-378; miR-378-5p; Skeletal muscle development
期刊名称：CELLULAR AND MOLECULAR LIFE SCIENCES （ 影响因子：6.2； 五年影响因子：7.7 ）
ISSN： 1420-682X
年卷期： 2024 年 81 卷 1 期
页码：
收录情况： SCI
摘要： Ythdf2 is known to mediate mRNA degradation in an m6A-dependent manner, and it has been shown to play a role in skeletal muscle differentiation. Recently, Ythdf2 was also found to bind to m6A-modified precursor miRNAs and regulate their maturation. However, it remains unknown whether this mechanism is related to the regulation of myogenesis by Ythdf2. Here, we observed that Ythdf2 knockdown significantly suppressed myotube formation and impacted miRNAs expression during myogenic differentiation. Through integrated analysis of miRNA and mRNA sequencing data, miR-378 and miR-378-5p were identified as important targets of Ythdf2 in myogenesis. Mechanically, Ythdf2 was found to interact with core components of the pre-miRNA processor complex, namely DICER1 and TARBP2, thereby facilitating the maturation of pre-miR-378/miR-378-5p in an m6A-dependent manner and resulting in an increase in the expression levels of mature miR-378 and miR-378-5p. Moreover, the downregulation of either miR-378 or miR-378-5p significantly inhibited myotube formation, while the forced expression of miR-378 or miR-378-5p could partially rescued Ythdf2 knockdown-induced suppression of myogenic differentiation by activating the mTOR pathway. Collectively, our results for the first time suggest that Ythdf2 regulates myogenic differentiation via mediating pre-miR-378/miR-378-5p maturation, which might provide new insights into the molecular mechanisms underlying m6A modification in the regulation of myogenesis.
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