Huang Huijun, Lu Geyan, Xiao Liyao, Tan Baohua, Yang Yuming, Hong Linjun, Li Zicong, Cai Gengyuan, Gu Ting
National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
Animals (Basel). 2025 Jul 5;15(13):1978. doi: 10.3390/ani15131978.
Skeletal muscle is the largest heterogeneous organ in the body, and multiple factors in intrinsic genetic and epigenetic regulation influence its growth. The N-methyladenosine ed(mA) modification is a conserved and most prevalent RNA modification, whose function is dependent on mA writers, erasers, and mA readers, such as the YTH protein family. YTHDC1 is the only member of the YTH protein family member that exists in the cell nucleus, which plays an important role in mRNA alternative polyadenylation and alternative splicing processes. However, the function of YTHDC1 in regulating myoblast proliferation, differentiation, and in vivo skeletal muscle development remains unclear. Therefore, in this study, we studied the function of YTHDC1 in C2C12 cell line and mouse. Our results showed that YTHDC1 significantly promoted myogenic differentiation while inhibiting myoblast proliferation in C2C12 cells, and the results of our in vivo experiment showed that interfering with YTHDC1 led to a significant enhancement of muscle growth in mice. Furthermore, the transcriptome sequencing analysis revealed that YTHDC1 might modulate skeletal muscle development by regulating alternative splicing of genes, including , , , and . Our study shed light on understanding the function and molecular mechanisms of YTHDC1 in regulating skeletal muscle development, highlighting the critical contribution of mA-mediated RNA splicing in muscle growth. These results indicated that YTHDC1 could be a potential breeding target gene to enhance meat quality in livestock.
骨骼肌是人体最大的异质性器官，内在遗传和表观遗传调控中的多种因素影响其生长。N-甲基腺苷（m6A）修饰是一种保守且最为普遍的RNA修饰，其功能依赖于m6A的写入器、擦除器以及m6A阅读蛋白，如YTH蛋白家族。YTHDC1是YTH蛋白家族中唯一存在于细胞核中的成员，在mRNA可变聚腺苷酸化和可变剪接过程中发挥重要作用。然而，YTHDC1在调节成肌细胞增殖、分化以及体内骨骼肌发育中的功能仍不清楚。因此，在本研究中，我们研究了YTHDC1在C2C12细胞系和小鼠中的功能。我们的结果表明，YTHDC1在C2C12细胞中显著促进成肌分化，同时抑制成肌细胞增殖，并且我们的体内实验结果表明，干扰YTHDC1会导致小鼠肌肉生长显著增强。此外，转录组测序分析表明，YTHDC1可能通过调节包括[此处原文缺失具体基因名称]等基因的可变剪接来调控骨骼肌发育。我们的研究为理解YTHDC1在调节骨骼肌发育中的功能和分子机制提供了线索，突出了m6A介导的RNA剪接在肌肉生长中的关键作用。这些结果表明，YTHDC1可能是提高家畜肉质的潜在育种目标基因。
