Regulation of m6A RNA Methylation and Its Effect on Myogenic Differentiation in Murine Myoblasts

Resumo

N⁶-methyladenosine (m⁶A) has been identified as a conserved epitranscriptomic modification of eukaryotic mRNAs, and plays important biological roles in the regulation of cellular metabolic processes. However, its role in myogenic differentiation is unclear. Here, we altered the m⁶A RNA methylation level by overexpression of METTL3, and explored the effect of m⁶A RNA methylation on myogenic differentiation of murine myoblasts in vitro. The m⁶A RNA methylation level is regulated by exogenous methylation inhibitor cycloleucine (Cyc) and methyl donor betaine (Bet). Therefore, chemical reagents of Cyc and Bet were used to test the regulatory effect of m⁶A RNA methylation on myogenic differentiation. Results showed that METTL3 and Bet positively regulated the m⁶A RNA methylation levels, and Cyc negatively regulated m⁶A RNA methylation levels. In addition, m⁶A methylation positively regulated myogenic differentiation in murine myoblasts. These findings provide insight in the mechanisms underlying the effect of m⁶A RNA methylation on myogenesis.