RNA-binding proteins Rbm38 and Rbm24 regulate myogenic differentiation via p21-dependent and -independent regulatory pathways
RNA-binding proteins Rbm38 and Rbm24 regulate myogenic differentiation via p21-dependent and -independent regulatory pathways
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DOI：
10.1111/j.1365-2443.2009.01347.x
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发表时间：
2009-11-01
期刊：
影响因子：
2.1
通讯作者：
Morisaki, Takayuki
中科院分区：
文献类型：
--
作者：
Miyamoto, Shoko;Hidaka, Kyoko;Morisaki, Takayuki
骨骼肌的分化需要有组织的一系列事件，包括增殖的成肌细胞的细胞周期停滞和细胞融合，从而导致多核肌管的形成。这一过程涉及对肌源性蛋白以及细胞周期相关蛋白基因表达的转录和转录后调控。RNA结合蛋白与靶RNA的特定序列结合，以转录后方式调节基因表达。然而，很少有组织特异性RNA结合蛋白被鉴定出来。在此，我们报道了RNA结合蛋白Rbm24和Rbm38在体外分化过程中在肌肉中优先表达。此外，通过RNA干扰抑制C2C12细胞的细胞周期停滞和延迟成肌分化。相反，过表达Rbm24或Rbm38可诱导细胞周期停滞，进而促进成肌细胞分化。用标记的RBM蛋白进行免疫沉淀-RT-PCR分析表明，Rbm38在体内与p21转录本结合。与此一致的是，p21的过度表达挽救了Rbm38基因敲除细胞的分化。综上所述，我们的结果表明，Rbm38通过与p21结合，在细胞周期停滞和肌源性分化中发挥关键作用。
Skeletal muscle differentiation entails organized sequential events, including cell cycle arrest of proliferating myoblast cells and cell fusion, which lead to the formation of multinucleated myotubes. This process involves both transcriptional and post-transcriptional regulation of the gene expression of myogenic proteins, as well as cell-cycle related proteins. RNA-binding proteins bind to specific sequences of target RNA and regulate gene expression in a post-transcriptional manner. However, few tissue-specific RNA binding proteins have been identified. Herein, we report that the RNA binding proteins Rbm24 and Rbm38 were found to be preferentially expressed in muscle during differentiation in vitro. Further, knockdown of either by RNA interference suppressed cell-cycle arrest and delayed myogenic differentiation in C2C12 cells. In contrast, over-expression of Rbm24 or Rbm38 induced cell cycle arrest, and then had a positive effect on myogenic differentiation. Immunoprecipitation-RT-PCR analysis using tagged Rbm proteins indicated that Rbm38 binds to the p21 transcript in vivo. Consistent with this, differentiation of Rbm38 knockdown cells was rescued by over-expression of p21. Together, our results suggest that Rbm38 plays a crucial role in cell cycle arrest and myogenic differentiation via its binding to p21.