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-介导的 circRNA 通过靶向核糖体蛋白 Rpl7 调节成肌细胞分化。

-Mediated circRNA Regulates Myogenesis by Targeting Ribosomal Protein Rpl7.

机构信息

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China.

Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen 518124, China.

出版信息

Genes (Basel). 2021 May 8;12(5):696. doi: 10.3390/genes12050696.

Abstract

Circular RNAs (circRNAs) represent a class of covalently closed single-stranded RNA molecules that are emerging as essential regulators of various biological processes. The circRNA originates from exon 2 of the gene in mice and was reported to be involved in acute promyelocytic leukemia and myocardial injury. However, the functions and mechanisms of in myogenesis are largely unknown. Here, to deepen our knowledge about the role of , we studied the expression and function of during skeletal myogenesis. We found that was mostly distributed in the cytoplasm, and dynamically and differentially expressed in various myogenesis systems in vitro and in vivo. Functionally, overexpression of inhibited myoblast proliferation and promoted myotube formation in C2C12 cells, whereas the opposite effects were observed after knockdown. Mechanistically, could directly bind to ribosomal protein Rpl7, an essential 60S preribosomal assembly factor, to inhibit ribosome translation. In addition, we verified that transcription factor directly bound to the promoter of and affected the expression of and in C2C12 myoblasts. Collectively, these findings identify as a candidate circRNA regulating ribosome biogenesis and myogenesis proliferation and differentiation.

摘要

环状 RNA(circRNAs)是一类共价闭合的单链 RNA 分子,作为各种生物学过程的重要调控因子而备受关注。环状 RNA 来源于小鼠基因的外显子 2,据报道参与急性早幼粒细胞白血病和心肌损伤。然而,环状 RNA 在肌生成中的功能和机制在很大程度上尚不清楚。在这里,为了加深我们对环状 RNA 作用的认识,我们研究了其在骨骼肌生成过程中的表达和功能。我们发现环状 RNA 主要分布在细胞质中,并在体外和体内各种肌生成系统中动态和差异表达。功能上,环状 RNA 的过表达抑制 C2C12 细胞中肌母细胞的增殖并促进肌管形成,而环状 RNA 敲低则观察到相反的效果。机制上,环状 RNA 可以直接与核糖体蛋白 Rpl7 结合,Rpl7 是一种必需的 60S 前核糖体组装因子,从而抑制核糖体翻译。此外,我们验证了转录因子 可以直接结合到环状 RNA 的启动子上,并影响 C2C12 肌母细胞中环状 RNA 和 的表达。总之,这些发现确定了环状 RNA 作为调节核糖体生物发生和肌生成增殖和分化的候选环状 RNA。

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