Effect of m6A Recognition Protein YTHDC1 on Skeletal Muscle Growth

Skeletal muscle is the largest heterogeneous organ in the body, and multiple factors in intrinsic genetic and epigenetic regulation influence its growth. The N⁶-methyladenosine ed(m⁶A) modification is a conserved and most prevalent RNA modification, whose function is dependent on m⁶A writers, erasers, and m⁶A 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 <i>Akap13</i>, <i>Smarca2</i>, <i>Tnnt3</i>, and <i>Neb</i>. Our study shed light on understanding the function and molecular mechanisms of YTHDC1 in regulating skeletal muscle development, highlighting the critical contribution of m⁶A-mediated RNA splicing in muscle growth. These results indicated that YTHDC1 could be a potential breeding target gene to enhance meat quality in livestock.