Circular RNA circMYBPC1 promotes skeletal muscle differentiation by targeting MyHC.
Circular RNA circMYBPC1 promotes skeletal muscle differentiation by targeting MyHC.
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环状RNA circMYBPC1通过靶向MyHC促进骨骼肌分化
DOI：
10.1016/j.omtn.2021.03.004
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发表时间：
2021-06-04
期刊：
影响因子：
--
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Chen M;Wei X;Song M;Jiang R;Huang K;Deng Y;Liu Q;Shi D;Li H
骨骼肌的发育是一个复杂的、高度协调的生物学过程，由一系列肌发生调控因子介导。大量研究表明，环状RNA（circRNA）参与肌肉分化，但涉及的确切分子机制尚不清楚。在此，我们分析了circRNA在牛最长肌成体和胚胎发育阶段的表达。鉴定了1，318个circRNA候选物的严格集合，并且我们发现495个circRNA在胚胎和成人组织文库之间差异表达。我们随后专注于一个最下调的circRNA（使用成人阶段表达作为对照），这被命名为肌肉分化相关环状RNA（circMYBPC 1）。通过RNA结合蛋白免疫沉淀（RIP）和RNA pull-down实验，证实了circMYBPC 1通过直接结合miR-23 a解除其对肌球蛋白重链（MyHC）的抑制而促进成肌细胞分化。RIP实验表明，circMYBPC 1可与MyHC蛋白直接结合。体内观察还表明，circMYBPC 1可能刺激肌肉损伤后的骨骼肌再生。这些结果表明，新的非编码circRNA circMYBPC 1促进成肌细胞的分化，并可能促进骨骼肌再生。我们的研究结果为深入分析circRNA在肌肉发生和肌肉疾病中的作用提供了基础。Chen等人通过RNA-seq鉴定了与安格斯牛肌肉发育相关的circRNA，并描述了牛骨骼肌中新环状RNA circMYBPC 1的发现和表征。通过分子生物学实验，他们发现circMYBPC 1与miR-23 a和MyHC蛋白相互作用，促进肌肉分化。
Skeletal muscle development is a complex and highly orchestrated biological process mediated by a series of myogenesis regulatory factors. Numerous studies have demonstrated that circular RNAs (circRNAs) are involved in muscle differentiation, but the exact molecular mechanisms involved remain unclear. Here, we analyzed the expression of circRNAs at the adult and embryo development stages of cattle musculus longissimus. A stringent set of 1,318 circRNAs candidates were identified, and we found that 495 circRNAs were differentially expressed between embryonic and adult tissue libraries. We subsequently focused on one of the most downregulated circRNAs (using the adult stage expression as control), and this was named muscle differentiation-associated circular RNA (circMYBPC1). With RNA binding protein immunoprecipitation (RIP) and RNA pull-down assays, circMYBPC1 was identified to promote myoblast differentiation by directly binding miR-23a to relieve its inhibition on myosin heavy chain (MyHC). In addition, RIP assays demonstrated that circMYBPC1 could directly bind MyHC protein. In vivo observations also suggested that circMYBPC1 may stimulate skeletal muscle regeneration after muscle damage. These results revealed that the novel non-coding circRNA circMYBPC1 promotes differentiation of myoblasts and may promote skeletal muscle regeneration. Our results provided a basis for in-depth analysis of the role of circRNA in myogenesis and muscle diseases. Chen et al. identified circRNAs related to Angus cattle muscle development through RNA-seq and described the discovery and characterization of a new circular RNA, circMYBPC1, in bovine skeletal muscle. Through molecular biology experiments, they found that circMYBPC1 interacts with miR-23a and MyHC proteins to promote muscle differentiation.
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