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Role of HuR in Skeletal Myogenesis through Coordinate Regulation of Muscle Differentiation Genes

机译:HuR在肌肉分化基因的协调调控中在骨骼肌新生中的作用。

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In this report, we investigate the role of the RNA-binding protein HuR during skeletal myogenesis. At the onset of myogenesis in differentiating C2C12 myocytes and in vivo in regenerating mouse muscle, HuR cytoplasmic abundance increased dramatically, returning to a predominantly nuclear presence upon completion of myogenesis. mRNAs encoding key regulators of myogenesis-specific transcription (myogenin and MyoD) and cell cycle withdrawal (p21), bearing AU-rich regions, were found to be targets of HuR in a differentiation-dependent manner. Accordingly, mRNA half-lives were highest during differentiation, declining when differentiation was completed. Importantly, HuR-overexpressing C2C12 cells displayed increased target mRNA expression and half-life and underwent precocious differentiation. Our findings underscore a critical function for HuR during skeletal myogenesis linked to HuR's coordinate regulation of muscle differentiation genes.
机译:在这份报告中,我们调查了骨骼肌发生过程中RNA结合蛋白HuR的作用。在分化C2C12心肌细胞的过程中发生肌肉形成的过程中以及再生小鼠肌肉的体内过程中,HuR的胞质丰度急剧增加,在完成肌肉形成过程后返回到主要为核的状态。编码肌发生特异性转录(肌生成素和MyoD)和细胞周期停滞(p21)的关键调控因子的mRNAs,以分化依赖的方式成为HuR的靶标,这些区域富含AU区域。因此,mRNA的半衰期在分化过程中最高,而在分化完成时下降。重要的是,过表达HuR的C2C12细胞显示出靶mRNA表达增加和半衰期增加,并经历了早熟分化。我们的发现强调了在HuR对肌肉分化基因的协调调节相关的骨骼肌形成过程中,HuR的关键功能。

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