METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C MRNA Stability in a MA-Dependent Manner

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Sep 28

PMID 37762418

Authors

Sen Zhao

Jiaxue Cao

Yanjin Sun

Helin Zhou

Qi Zhu

Dinghui Dai

Siyuan Zhan

Jiazhong Guo

Tao Zhong

Linjie Wang

Li Li

Hongping Zhang

Affiliations

Soon will be listed here.

Abstract

The development of mammalian skeletal muscle is a highly complex process involving multiple molecular interactions. As a prevalent RNA modification, N6-methyladenosine (mA) regulates the expression of target genes to affect mammalian development. Nevertheless, it remains unclear how mA participates in the development of goat muscle. In this study, methyltransferase 3 (METTL3) was significantly enriched in goat longissimus dorsi (LD) tissue. In addition, the global mA modification level and differentiation of skeletal muscle satellite cells (MuSCs) were regulated by METTL3. By performing mRNA-seq analysis, 8050 candidate genes exhibited significant changes in expression level after the knockdown of METTL3 in MuSCs. Additionally, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that myocyte enhancer factor 2c (MEF2C) mRNA contained mA modification. Further experiments demonstrated that METTL3 enhanced the differentiation of MuSCs by upregulating mA levels and expression of MEF2C. Moreover, the mA reader YTH N6-methyladenosine RNA binding protein C1 (YTHDC1) was bound and stabilized to mRNA. The present study reveals that METTL3 enhances myogenic differentiation in MuSCs by regulating MEF2C and provides evidence of a post-transcriptional mechanism in the development of goat skeletal muscle.

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