Natural antisense transcript of MYOG regulates development and regeneration in skeletal muscle by shielding the binding sites of MicroRNAs of MYOG mRNA 3'UTR
Natural antisense transcript of MYOG regulates development and regeneration in skeletal muscle by shielding the binding sites of MicroRNAs of MYOG mRNA 3'UTR
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DOI：
10.1016/j.bbrc.2023.04.050
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发表时间：
2023-04-25
影响因子：
3.1
通讯作者：
Luo，Wen
中科院分区：
文献类型：
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作者：
Yin，Yunqian;Chen，Genghua;Luo，Wen
自然反义转录本(NAT)是与正义转录本相反的内源性RNA，它们可以通过多种表观遗传机制对调节各种生物学过程做出重要贡献。NAT可以影响它们的正义转录，从而调节骨骼肌的生长和发育。我们对第三代全长转录组测序数据的分析表明，NAT在lncRNA中占很大比例，占30.19%-33.35%。NAT的表达与成肌细胞的分化有关，表达NAT的基因主要参与RNA合成、蛋白质转运和细胞周期。我们在数据中发现了MYOG的NAT(MYOG-NAT)。我们发现MYOG-NAT在体外可以促进成肌细胞的分化。此外，在体内敲除MYOG-NAT会导致肌肉纤维萎缩和肌肉再生迟缓。分子生物学实验表明，MYOG-NAT通过与miR-128-2-5p、miR-19a-5p和miR-19b-5p竞争结合MYOGmRNA3‘非编码区来增强MYOGmRNA的稳定性。这些发现表明MYOG-NAT在骨骼肌发育中起着关键作用，并为NAT的转录后调控提供了见解。
Natural antisense transcripts (NATs) are endogenous RNAs opposite to sense transcripts, and they can significantly contribute to regulating various biological processes through multiple epigenetic mechanisms. NATs can affect their sense transcripts to regulate the growth and development of skeletal muscle. Our analysis of third-generation full-length transcriptome sequencing data revealed that NATs represented a significant portion of the lncRNA, accounting for up to 30.19%–33.35%. The expression of NATs correlated with myoblast differentiation, and genes expressing NATs were mainly involved in RNA synthesis, protein transport, and cell cycle. We found a NAT ofMYOG(MYOG-NAT) in the data. We found that the MYOG-NAT could promote the differentiation of myoblasts in vitro. Additionally, knockdown of MYOG-NAT in vivo led to muscle fiber atrophy and muscle regeneration retardation. Molecular biology experiments demonstrated that MYOG-NAT enhances the stability ofMYOGmRNA by competing with miR-128-2-5p, miR-19a-5p, and miR-19b-5p for binding toMYOGmRNA 3′UTR. These findings suggest that MYOG-NAT plays a critical role in skeletal muscle development and provides insights into the post-transcriptional regulation of NATs.