MEF2C Expression Is Regulated by the Post-transcriptional Activation of the METTL3-m6A-YTHDF1 Axis in Myoblast Differentiation

Xinran Yang; Yue Ning; Sayed Haidar Abbas Raza; Chugang Mei; Linsen Zan

doi:10.3389/fvets.2022.900924

MEF2C Expression Is Regulated by the Post-transcriptional Activation of the METTL3-m⁶A-YTHDF1 Axis in Myoblast Differentiation

Front Vet Sci. 2022 Apr 28:9:900924. doi: 10.3389/fvets.2022.900924. eCollection 2022.

Authors

Xinran Yang¹, Yue Ning^{1

2}, Sayed Haidar Abbas Raza¹, Chugang Mei^{1

3}, Linsen Zan^{1

3}

Affiliations

¹ College of Animal Science and Technology, Northwest A&F University, Xianyang, China.
² College of Chemistry and Chemical Engineering, Xianyang Normal University, Xianyang, China.
³ National Beef Cattle Improvement Center, Northwest A&F University, Xianyang, China.

Abstract

N ⁶-methyladenosine (m⁶A) plays an essential role in regulating gene expression. However, the effect of m⁶A on skeletal myoblast differentiation and the underlying mechanisms are still unclear. Here, we ascertained mRNA m⁶A methylation exhibited declined changes during bovine skeletal myoblast differentiation, and both MEF2C mRNA expression and m⁶A levels were significantly increased during myoblast differentiation. We found that MEF2C with mutated m⁶A sites significantly inhibited myoblast differentiation compared with wild-type MEF2C. METTL3 promoted MEF2C protein expression through posttranscriptional modification in an m⁶A-YTHDF1-dependent manner. Moreover, MEF2C promoted the expression of METTL3 by binding to its promoter. These results revealed that there is a positive feedback loop between these molecules in myoblast differentiation. Our study provided new insights into skeletal muscle differentiation and fusion, which may provide an RNA methylation-based approach for molecular genetics and breeding in livestock as well as for the treatment of muscle-related diseases.

Keywords: MEF2C; METTL3; N6-methyladenosine; cattle; myoblast differentiation.