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METTL3通过以m⁶A依赖的方式调节MEF2C mRNA稳定性促进山羊骨骼肌卫星细胞分化。

METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C mRNA Stability in a mA-Dependent Manner.

作者信息

Zhao Sen, Cao Jiaxue, Sun Yanjin, Zhou Helin, Zhu Qi, Dai Dinghui, Zhan Siyuan, Guo Jiazhong, Zhong Tao, Wang Linjie, Li Li, Zhang Hongping

机构信息

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.

Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, China.

出版信息

Int J Mol Sci. 2023 Sep 14;24(18):14115. doi: 10.3390/ijms241814115.


DOI:10.3390/ijms241814115
PMID:37762418
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10531580/
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.

摘要

哺乳动物骨骼肌的发育是一个高度复杂的过程,涉及多种分子相互作用。作为一种普遍存在的RNA修饰,N6-甲基腺苷(m6A)调节靶基因的表达以影响哺乳动物的发育。然而,m6A如何参与山羊肌肉的发育仍不清楚。在本研究中,甲基转移酶3(METTL3)在山羊背最长肌(LD)组织中显著富集。此外,METTL3调节骨骼肌卫星细胞(MuSCs)的整体m6A修饰水平和分化。通过进行mRNA测序分析,在MuSCs中敲低METTL3后,8050个候选基因的表达水平发生了显著变化。此外,甲基化RNA免疫沉淀测序(MeRIP-seq)表明肌细胞增强因子2c(MEF2C)mRNA含有m6A修饰。进一步的实验表明,METTL3通过上调m6A水平和MEF2C的表达来增强MuSCs的分化。此外,m6A阅读蛋白YTH N6-甲基腺苷RNA结合蛋白C1(YTHDC1)与mRNA结合并使其稳定。本研究揭示了METTL3通过调节MEF2C增强MuSCs的成肌分化,并为山羊骨骼肌发育中的转录后机制提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/2f7677513c21/ijms-24-14115-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/020d1bc1add1/ijms-24-14115-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/c7b9b233a3f9/ijms-24-14115-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/f291c5cc57b6/ijms-24-14115-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/0b8ceb30054f/ijms-24-14115-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/aa14ba4c65fa/ijms-24-14115-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/2f7677513c21/ijms-24-14115-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/020d1bc1add1/ijms-24-14115-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/c7b9b233a3f9/ijms-24-14115-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/f291c5cc57b6/ijms-24-14115-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/0b8ceb30054f/ijms-24-14115-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/aa14ba4c65fa/ijms-24-14115-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33a9/10531580/2f7677513c21/ijms-24-14115-g006.jpg

相似文献

[1]
METTL3 Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating MEF2C mRNA Stability in a mA-Dependent Manner.

Int J Mol Sci. 2023-9-14

[2]
MEF2C Expression Is Regulated by the Post-transcriptional Activation of the METTL3-mA-YTHDF1 Axis in Myoblast Differentiation.

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[3]
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[4]
A defined N6-methyladenosine (mA) profile conferred by METTL3 regulates muscle stem cell/myoblast state transitions.

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[5]
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[6]
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[7]
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[8]
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[9]
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Life Sci. 2022-6-1

[10]
Dynamic mA mRNA Methylation Reveals the Role of METTL3/14-mA-MNK2-ERK Signaling Axis in Skeletal Muscle Differentiation and Regeneration.

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引用本文的文献

[1]
METTL3-dependent mA modification of GHR mRNA regulates mitochondrial function through mitochondrial biogenesis during myoblast differentiation.

Poult Sci. 2025-7

[2]
The m6A modification regulates the composition of myofiber types in chicken skeletal muscle.

Poult Sci. 2025-3

[3]
microRNA Temporal-Specific Expression Profiles Reveal longissimus dorsi Muscle Development in Tianzhu White Yak.

Int J Mol Sci. 2024-9-21

[4]
Fat Mass- and Obesity-Associated Protein (FTO) Promotes the Proliferation of Goat Skeletal Muscle Satellite Cells by Stabilizing DAG1 mRNA in an IGF2BP1-Related mA Manner.

Int J Mol Sci. 2024-9-11

[5]
Research Progress on the Role of M6A in Regulating Economic Traits in Livestock.

Int J Mol Sci. 2024-7-31

[6]
An Identification of Functional Genetic Variants in Gene and Their Association with Growth Traits in Goats.

Genes (Basel). 2024-3-3

本文引用的文献

[1]
HuR Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating Myomaker mRNA Stability.

Int J Mol Sci. 2023-4-7

[2]
METTL3-mediated m6A modification stabilizes TERRA and maintains telomere stability.

Nucleic Acids Res. 2022-11-11

[3]
Interactive regulation of DNA demethylase gene TET1 and mA methyltransferase gene METTL3 in myoblast differentiation.

Int J Biol Macromol. 2022-12-31

[4]
CircTCF4 Suppresses Proliferation and Differentiation of Goat Skeletal Muscle Satellite Cells Independent from AGO2 Binding.

Int J Mol Sci. 2022-10-25

[5]
Transcriptional and functional consequences of alterations to MEF2C and its topological organization in neuronal models.

Am J Hum Genet. 2022-11-3

[6]
Physicochemical property, bacterial diversity, and volatile profile during ripening of naturally fermented dry mutton sausage produced from Jianzhou big-eared goat.

Front Microbiol. 2022-9-2

[7]
mA Methylases Regulate Myoblast Proliferation, Apoptosis and Differentiation.

Animals (Basel). 2022-3-18

[8]
The m6A reader IGF2BP3 promotes acute myeloid leukemia progression by enhancing RCC2 stability.

Exp Mol Med. 2022-2

[9]
scDART-seq reveals distinct mA signatures and mRNA methylation heterogeneity in single cells.

Mol Cell. 2022-2-17

[10]
Effect of dietary buriti oil on the quality, fatty acid profile and sensorial attributes of lamb meat.

Meat Sci. 2022-4

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