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METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C mRNA Stability in a m(6)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(6)A) regulates the expression of target genes to affect mammalian development. Nevertheless, it remains unclear how m(6)A partici...

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Autores principales: Zhao, Sen, Cao, Jiaxue, Sun, Yanjin, Zhou, Helin, Zhu, Qi, Dai, Dinghui, Zhan, Siyuan, Guo, Jiazhong, Zhong, Tao, Wang, Linjie, Li, Li, Zhang, Hongping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531580/
https://www.ncbi.nlm.nih.gov/pubmed/37762418
http://dx.doi.org/10.3390/ijms241814115
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author Zhao, Sen
Cao, Jiaxue
Sun, Yanjin
Zhou, Helin
Zhu, Qi
Dai, Dinghui
Zhan, Siyuan
Guo, Jiazhong
Zhong, Tao
Wang, Linjie
Li, Li
Zhang, Hongping
author_facet Zhao, Sen
Cao, Jiaxue
Sun, Yanjin
Zhou, Helin
Zhu, Qi
Dai, Dinghui
Zhan, Siyuan
Guo, Jiazhong
Zhong, Tao
Wang, Linjie
Li, Li
Zhang, Hongping
author_sort Zhao, Sen
collection PubMed
description The development of mammalian skeletal muscle is a highly complex process involving multiple molecular interactions. As a prevalent RNA modification, N6-methyladenosine (m(6)A) regulates the expression of target genes to affect mammalian development. Nevertheless, it remains unclear how m(6)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(6)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(6)A modification. Further experiments demonstrated that METTL3 enhanced the differentiation of MuSCs by upregulating m(6)A levels and expression of MEF2C. Moreover, the m(6)A reader YTH N6-methyladenosine RNA binding protein C1 (YTHDC1) was bound and stabilized to MEF2C 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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spelling pubmed-105315802023-09-28 METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C mRNA Stability in a m(6)A-Dependent Manner Zhao, Sen Cao, Jiaxue Sun, Yanjin Zhou, Helin Zhu, Qi Dai, Dinghui Zhan, Siyuan Guo, Jiazhong Zhong, Tao Wang, Linjie Li, Li Zhang, Hongping Int J Mol Sci Article The development of mammalian skeletal muscle is a highly complex process involving multiple molecular interactions. As a prevalent RNA modification, N6-methyladenosine (m(6)A) regulates the expression of target genes to affect mammalian development. Nevertheless, it remains unclear how m(6)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(6)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(6)A modification. Further experiments demonstrated that METTL3 enhanced the differentiation of MuSCs by upregulating m(6)A levels and expression of MEF2C. Moreover, the m(6)A reader YTH N6-methyladenosine RNA binding protein C1 (YTHDC1) was bound and stabilized to MEF2C 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. MDPI 2023-09-14 /pmc/articles/PMC10531580/ /pubmed/37762418 http://dx.doi.org/10.3390/ijms241814115 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Sen
Cao, Jiaxue
Sun, Yanjin
Zhou, Helin
Zhu, Qi
Dai, Dinghui
Zhan, Siyuan
Guo, Jiazhong
Zhong, Tao
Wang, Linjie
Li, Li
Zhang, Hongping
METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C mRNA Stability in a m(6)A-Dependent Manner
title METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C mRNA Stability in a m(6)A-Dependent Manner
title_full METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C mRNA Stability in a m(6)A-Dependent Manner
title_fullStr METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C mRNA Stability in a m(6)A-Dependent Manner
title_full_unstemmed METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C mRNA Stability in a m(6)A-Dependent Manner
title_short METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C mRNA Stability in a m(6)A-Dependent Manner
title_sort mettl3 promotes the differentiation of goat skeletal muscle satellite cells by regulating mef2c mrna stability in a m(6)a-dependent manner
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531580/
https://www.ncbi.nlm.nih.gov/pubmed/37762418
http://dx.doi.org/10.3390/ijms241814115
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