Stage-specific requirement for Mettl3-dependent m6A epitranscriptomic regulation during myogenesis [RNA-Seq]

The role of N6-methyladenosine (m6A) in muscle formation and maintenance remains incompletely understood, particularly with respect to the contribution of methyltransferase-like 3 (METTL3), the core component of the methyltransferase complex (MTC), to myogenesis. Here, we show the involvement of METTL3 in the m6A epitranscriptome during myogenesis. Our findings reveal a correlation between METTL3-regulated m6A modifications and myoblast fusion during differentiation and regeneration. We observed significant upregulation of METTL3 following injury and identified numerous alterations in myogenic pathways. Furthermore, we detected differential patterns of METTL3-regulated m6A modifications in genes during differentiation, with some genes exhibiting loss and others showing gain. Our study revealed that the fusion factors Mymx and Mymk are downstream elements of METTL3 involved in myogenesis, and both exhibit upregulated expression and m6A levels during myogenesis. Our findings provide valuable resources for elucidating the function and mechanism of METTL3-regulated m6A modifications in myogenesis, thereby revealing the regulatory role of METTL3 in myoblast fusion. Overall design: RNA-seq profiling of wildtype C2C12 cells and their overexpressed derivatives at Day0 and Day4 of myoblasts differentiation.RNA-seq profiling of wildtype C2C12 cells and their knockout derivatives at Day0 and Day3 of myoblasts differentiation.