N6-methyladenosine (m6A) modification plays a critical role in mammalian 
development. However, the role of m6A in the skeletal muscle development remains 
largely unknown. Here, we report a global m6A modification pattern of goat 
skeletal muscle at two key development stages and identified that the m6A 
modification regulated the expression of the growth arrest and DNA 
damage-inducible 45B (GADD45B) gene, which is involved in myogenic 
differentiation. We showed that GADD45B expression increased during myoblast 
differentiation, whereas the downregulation of GADD45B inhibits myogenic 
differentiation and mitochondrial biogenesis. Moreover, the expression of 
GADD45B regulates the expression of myogenic regulatory factors and peroxisome 
proliferator-activated receptor gamma coactivator 1 alpha by activating the p38 
mitogen-activated protein kinase (MAPK) pathway. Conversely, the inactivation of 
p38 MAPK abolished the GADD45B-mediated myogenic differentiation. Furthermore, 
we found that the knockdown of fat mass and obesity-associated protein (FTO) 
increases GADD45B m6A modification and decreases the stability of GADD45B mRNA, 
which impairs myogenic differentiation. Our results indicate that the 
FTO-mediated m6A modification in GADD45B mRNA drives skeletal muscle 
differentiation by activating the p38 MAPK pathway, which provides a molecular 
mechanism for the regulation of myogenesis via RNA methylation.