Regulatory role of RNA N6-methyladenosine modifications during skeletal muscle development

Yu, Baojun; Liu, Shiyuan; Zhang, Juan; Mu, Tong; Feng, Xiaobing; Ma, Ruoshuang; Gu, Yan

doi:10.3389/fcell.2022.929183

Cited by 11 publications

(7 citation statements)

References 135 publications

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“…As the most abundant RNA modification, m 6 A modification plays an important role in skeletal muscle development [ 19 , 31 ]. However, ALKBH5 is a well-known demethylase that has rarely been reported to regulate skeletal muscle development.…”

Section: Discussionmentioning

confidence: 99%

MYH1G-AS is a chromatin-associated lncRNA that regulates skeletal muscle development in chicken

Cai,

Ma,

Yuan

et al. 2024

Cell Mol Biol Lett

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Background Skeletal muscle development is pivotal for animal growth and health. Recently, long noncoding RNAs (lncRNAs) were found to interact with chromatin through diverse roles. However, little is known about how lncRNAs act as chromatin-associated RNAs to regulate skeletal muscle development. Here, we aim to investigate the regulation of chromatin-associated RNA (MYH1G-AS) during skeletal muscle development. Methods We provided comprehensive insight into the RNA profile and chromatin accessibility of different myofibers, combining RNA sequencing (RNA-seq) with an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). The dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were used to analyze the transcriptional regulation mechanism of MYH1G-AS. ALKBH5-mediated MYH1G-AS N6-methyladenosine (m6A) demethylation was assessed by a single-base elongation and ligation-based qPCR amplification method (SELECT) assay. Functions of MYH1G-AS were investigated through a primary myoblast and lentivirus/cholesterol-modified antisense oligonucleotide (ASO)-mediated animal model. To validate the interaction of MYH1G-AS with fibroblast growth factor 18 (FGF18) protein, RNA pull down and an RNA immunoprecipitation (RIP) assay were performed. Specifically, the interaction between FGF18 and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5) protein was analyzed by coimmunoprecipitation (Co-IP) and a yeast two-hybrid assay. Results A total of 45 differentially expressed (DE) lncRNAs, with DE ATAC-seq peaks in their promoter region, were classified as open chromatin-associated lncRNAs. A skeletal muscle-specific lncRNA (MSTRG.15576.9; MYH1G-AS), which is one of the open chromatin-associated lncRNA, was identified. MYH1G-AS transcription is coordinately regulated by transcription factors (TF) SMAD3 and SP2. Moreover, SP2 represses ALKBH5 transcription to weaken ALKBH5-mediated m6A demethylation of MYH1G-AS, thus destroying MYH1G-AS RNA stability. MYH1G-AS accelerates myoblast proliferation but restrains myoblast differentiation. Moreover, MYH1G-AS drives a switch from slow-twitch to fast-twitch fibers and causes muscle atrophy. Mechanistically, MYH1G-AS inhibits FGF18 protein stabilization to reduce the interaction of FGF18 to SMARCA5, thus repressing chromatin accessibility of the SMAD4 promoter to activate the SMAD4-dependent pathway. Conclusions Our results reveal a new pattern of the regulation of lncRNA expression at diverse levels and help expound the regulation of m6A methylation on chromatin status. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

MYH1G-AS is a chromatin-associated lncRNA that regulates skeletal muscle development in chicken

Cai,

Ma,

Yuan

et al. 2024

Cell Mol Biol Lett

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“…Studies have shown that FTO and YTHDF2 can act in opposition to regulate the fate of m6A-modified mRNA. 37 More importantly, FTO has been identified to interact with YTHDF2 during the development of human cancers. For example, in an m6A-YTHDF2-dependent way, FTO facilitates the advancement of multiple myeloma by promoting the posttranscriptional activation of HSF1.…”

Section: Discussionmentioning

confidence: 99%

“…Herein, we demonstrated that FTO suppressed the enrichment of m6A‐modified LINC01559 mRNAs, leading to the upregulation of LINC01559 in BCa. Studies have shown that FTO and YTHDF2 can act in opposition to regulate the fate of m6A‐modified mRNA 37 . More importantly, FTO has been identified to interact with YTHDF2 during the development of human cancers.…”

Section: Discussionmentioning

confidence: 99%

FTO‐mediated epigenetic upregulation of LINC01559 confers cell resistance to docetaxel in breast carcinoma by suppressing miR‐1343‐3p

Lin

Kong

et al. 2023

The Kaohsiung J of Med Scie

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This study was to explore the regulatory effect of long non‐coding RNA LINC01559 on Docetaxel resistance in breast carcinoma (BCa) and its underlying mechanism. In the present study, we found that LINC01559 expression was elevated and LINC01559 overexpression facilitated docetaxel resistance in BCa cells. Moreover, it was revealed that the upregulation of LINC01559 in BCa cells was induced by FTO‐mediated demethylation in an m6A‐YTHDF2‐dependent manner. Additionally, Dual‐luciferase reporter assay confirmed the binding ability between LINC01559 and miR‐1343‐3p, and Pearson correlation analysis showed a negative correlation between them. Particularly, miR‐1343‐3p inhibition partly abolished the suppression on docetaxel resistance in BCa cells caused by LINC01559 knockdown. To sum up, FTO‐mediated epigenetic upregulation of LINC01559 promoted cell resistance to Docetaxel in BCa by negatively regulating miR‐1343‐3p.

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“…In recent years, m 6 A has been one of the hot topics in various mammalian organ development, including embryo development [ 15 ], neurogenesis [ 16 ], adipogenesis [ 17 ], and skeletal muscle development [ 18 ]. Several studies have demonstrated that m 6 A controls myoblast proliferation and differentiation by post-transcriptional regulating the expression of key muscle-specific transcription factors [ 19 , 20 ]. As an important regulator of skeletal muscle development, TGFβ1 is regulated by a variety of genetic and epigenetic factors [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Targeted Demethylation of the TGFβ1 mRNA Promotes Myoblast Proliferation via Activating the SMAD2 Signaling Pathway

Deng

Liu

et al. 2023

Cells

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Recent evidence suggested that N6-methyladenosine (m6A) methylation can determine m6A-modified mRNA fate and play an important role in skeletal muscle development. It was well known that transforming growth factor beta 1 (TGFβ1) is involved in a variety of cellular processes, such as proliferation, differentiation, and apoptosis. However, little is known about the m6A-mediated TGFβ1 regulation in myogenesis. Here, we observed an increase in endogenous TGFβ1 expression and activity during myotube differentiation. However, the knockdown of TGFβ1 inhibits the proliferation and induces cell apoptosis of myoblast. Moreover, we found that m6A in 5′-untranslated regions (5′UTR) of TGFβ1 promote its decay and inhibit its expression, leading to the blockage of the TGFβ1/SMAD2 signaling pathway. Furthermore, the targeted specific demethylation of TGFβ1 m6A using dCas13b-FTO significantly increased the TGFβ1-mediated activity of the SMAD2 signaling pathway, promoting myoblast proliferation. These findings suggest that TGFβ1 is an essential regulator of myoblast growth that is negatively regulated by m6A. Overall, these results highlight the critical role of m6A-mediated post-transcriptional regulation in myogenesis.

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Regulatory role of RNA N6-methyladenosine modifications during skeletal muscle development

Cited by 11 publications

References 135 publications

MYH1G-AS is a chromatin-associated lncRNA that regulates skeletal muscle development in chicken

MYH1G-AS is a chromatin-associated lncRNA that regulates skeletal muscle development in chicken

FTO‐mediated epigenetic upregulation of LINC01559 confers cell resistance to docetaxel in breast carcinoma by suppressing miR‐1343‐3p

Targeted Demethylation of the TGFβ1 mRNA Promotes Myoblast Proliferation via Activating the SMAD2 Signaling Pathway

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