COPS3 AS lncRNA 增强成肌分化并维持快型肌管表型。
COPS3 AS lncRNA enhances myogenic differentiation and maintains fast-type myotube phenotype.
机构信息
Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, China.
Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, China.
出版信息
Cell Signal. 2022 Jul;95:110341. doi: 10.1016/j.cellsig.2022.110341. Epub 2022 Apr 28.
Long non-coding RNAs (lncRNAs) play essential roles in myogenesis. Here, we identified a novel long non-coding RNA, named COPS3 AS lncRNA (COP9 signalosome complex subunit 3 antisense lncRNA), which was transcribed from the mouse COPS3 gene antisense strand and highly expressed in glycolytic muscle fibers. Functionally, COPS3 AS lncRNA knockdown inhibited myogenic differentiation in myoblasts, whereas its overexpression promoted the process. Moreover, COPS3 AS lncRNA maintained the fast-twitch myotubes phenotype. Mechanistically, although COPS3 AS lncRNA did not form AS lncRNA/mRNA dimer with COPS3 mRNA, it as a competing endogenous RNA (ceRNA) to sponge miR-762, promoted myogenic differentiation and Fast-MyHC expression by modulating miR-762 target gene myogenic differentiation 1 (MyoD1). Taken together, COPS3 AS lncRNA is a key candidate regulator of myogenesis and fast-MyHC myotubes specification by miR-762/MyoD signalling axis.
长非编码 RNA（lncRNAs）在肌肉发生中发挥重要作用。在这里，我们鉴定了一种新的长非编码 RNA，命名为 COPS3 AS lncRNA（COPS9 信号小体复合物亚基 3 反义 lncRNA），它由小鼠 COPS3 基因反义链转录而来，在糖酵解肌纤维中高度表达。功能上，COPS3 AS lncRNA 的敲低抑制了成肌细胞的肌生成分化，而其过表达则促进了该过程。此外，COPS3 AS lncRNA 维持快肌纤维的表型。在机制上，尽管 COPS3 AS lncRNA 没有与 COPS3 mRNA 形成 AS lncRNA/mRNA 二聚体，但它作为竞争性内源 RNA（ceRNA）来吸附 miR-762，通过调节 miR-762 的靶基因肌细胞生成蛋白 1（MyoD1）促进肌生成分化和快肌肌球蛋白重链（Fast-MyHC）的表达。总之，COPS3 AS lncRNA 是肌生成和快肌肌纤维特化的关键候选调节因子，通过 miR-762/MyoD 信号通路发挥作用。
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