RNA-binding motif protein 24 regulates myogenin expression and promotes myogenic differentiation
RNA-binding motif protein 24 regulates myogenin expression and promotes myogenic differentiation
复制标题
DOI：
10.1111/j.1365-2443.2010.01446.x
复制
发表时间：
2010-11-01
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：
Jin, Donghao;Hidaka, Kyoko;Morisaki, Takayuki
肌纤维的形成涉及许多蛋白质的顺序表达，这些蛋白质调节成肌细胞向肌管转变期间的关键步骤。肌细胞生成素是小鼠成肌细胞系C2 C12中肌细胞分化的启动和维持的主要参与者。RNA结合蛋白与特定的靶RNA序列结合，以转录后方式调节基因表达。这项研究表明，RNA结合基序蛋白24（Rbm 24）与肌细胞生成素mRNA的3 '-非翻译区相互作用，并影响其在C2 C12肌细胞生成中的半衰期。通过RNA干扰敲低Rbm 24表达显著降低了与抑制肌生成相关的肌生成素表达。相反，通过稳定转染质粒过表达Rbm 24增加了肌细胞生成素的表达，并对肌细胞分化有积极作用。肌细胞生成素的异位表达也能够恢复Rbm 24敲低细胞的肌细胞分化。总之，我们的研究结果表明，Rbm 24结合肌细胞生成素mRNA，并调节其在C2 C12细胞中的稳定性。rbm 24至少部分通过肌细胞生成素依赖的转录后调节途径在肌细胞分化中起关键作用。
The formation of muscle fibers involves sequential expression of many proteins that regulate key steps during myoblast-to-myotube transition. Myogenin is a major player in the initiation and maintenance of myogenic differentiation in a mouse myoblast cell line, C2C12. RNA-binding proteins bind to specific target RNA sequences and regulate gene expression in a post-transcriptional manner. This study demonstrates that RNA-binding motif protein 24 (Rbm24) interacts with the 3'-untranslated region of myogenin mRNA and affects its half-life in C2C12 myogenesis. Knockdown of Rbm24 expression by RNA interference significantly decreased myogenin expression associated with the inhibition of myogenesis. In contrast, the overexpression of Rbm24 by stable transfection of a plasmid increased myogenin expression and had a positive effect on myogenic differentiation. Ectopic expression of myogenin was also able to restore myogenic differentiation in Rbm24-knockdown cells. Together, our results suggest that Rbm24 binds to myogenin mRNA and regulates its stability in C2C12 cells. Rbm24 plays a crucial role in myogenic differentiation at least in part through a myogenin-dependent post-transcriptional regulatory pathway.