The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation
The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation
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DOI：
10.1016/j.devcel.2006.08.003
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发表时间：
2006-10-01
影响因子：
11.8
通讯作者：
Sartorelli, Vittorio
中科院分区：
文献类型：
--
作者：
Caretti, Giuseppina;Schiltz, R. Louis;Sartorelli, Vittorio
MyoD调节骨骼肌发生。由于与MyoD相关的蛋白质发挥调控功能，它们的鉴定有望为骨骼肌基因表达调控机制的研究提供重要见解。我们已经发现RNA解旋酶p68/p72是MyoD相关蛋白，并且非编码RNA SRA也与MyoD免疫沉淀。体内外实验表明，p68/p72和SRA都是MyoD的共激活因子。对p68/p72或SRA的RNA干扰阻止了肌肉基因表达和细胞分化的适当激活。出乎意料的是，降低p68/p72蛋白的水平损害了TATA结合蛋白TBP、RNA聚合酶II和ATP酶SWI/SNF复合物的催化亚基Brg-1的募集，并阻碍了染色质重塑。这些发现揭示了p68/p72在促进转录起始复合物形成和染色质重塑所需的蛋白质组装中起关键作用。
MyoD regulates skeletal myogenesis. Since proteins associated with MyoD exert regulatory functions, their identification is expected to contribute important insights into the mechanisms governing gene expression in skeletal muscle. We have found that the RNA helicases p68/p72 are MyoD-associated proteins and that the noncoding RNA SRA also immunoprecipitates with MyoD. In vitro and in vivo experiments indicated that both p68/p72 and SRA are coactivators of MyoD. RNA interference toward either p68/p72 or SRA prevented proper activation of muscle gene expression and cell differentiation. Unexpectedly, reducing the levels of p68/p72 proteins impaired recruitment of the TATA binding protein TBP; RNA polymerase II; and the catalytic subunit of the ATPase SWI/SNF complex, Brg-1, and hindered chromatin remodeling. These findings reveal that p68/p72 play a critical role in promoting the assembly of proteins required for the formation of the transcription initiation complex and chromatin remodeling.