METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C mRNA Stability in a m<sup>6</sup>A-Dependent Manner
The development of mammalian skeletal muscle is a highly complex process involving multiple molecular interactions. As a prevalent RNA modification, N6-methyladenosine (m<sup>6</sup>A) regulates the expression of target genes to affect mammalian development. Nevertheless, it remains uncl...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/18/14115 |
| Summary: | The development of mammalian skeletal muscle is a highly complex process involving multiple molecular interactions. As a prevalent RNA modification, N6-methyladenosine (m<sup>6</sup>A) regulates the expression of target genes to affect mammalian development. Nevertheless, it remains unclear how m<sup>6</sup>A 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 m<sup>6</sup>A 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 m<sup>6</sup>A modification. Further experiments demonstrated that METTL3 enhanced the differentiation of MuSCs by upregulating m<sup>6</sup>A levels and expression of MEF2C. Moreover, the m<sup>6</sup>A reader YTH N6-methyladenosine RNA binding protein C1 (YTHDC1) was bound and stabilized to <i>MEF2C</i> 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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| ISSN: | 1661-6596 1422-0067 |