SON 通过协调调控 RNA 剪接控制细胞周期进程。
SON controls cell-cycle progression by coordinated regulation of RNA splicing.
机构信息
Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
出版信息
Mol Cell. 2011 Apr 22;42(2):185-98. doi: 10.1016/j.molcel.2011.03.014.
It has been suspected that cell-cycle progression might be functionally coupled with RNA processing. However, little is known about the role of the precise splicing control in cell-cycle progression. Here, we report that SON, a large Ser/Arg (SR)-related protein, is a splicing cofactor contributing to efficient splicing of cell-cycle regulators. Downregulation of SON leads to severe impairment of spindle pole separation, microtubule dynamics, and genome integrity. These molecular defects result from inadequate RNA splicing of a specific set of cell-cycle-related genes that possess weak splice sites. Furthermore, we show that SON facilitates the interaction of SR proteins with RNA polymerase II and other key spliceosome components, suggesting its function in efficient cotranscriptional RNA processing. These results reveal a mechanism for controlling cell-cycle progression through SON-dependent constitutive splicing at suboptimal splice sites, with strong implications for its role in cancer and other human diseases.
人们一直怀疑细胞周期进程可能与 RNA 处理在功能上偶联。然而，对于精确剪接控制在细胞周期进程中的作用知之甚少。在这里，我们报告说，SON，一种大的 Ser/Arg（SR）相关蛋白，是一种剪接辅助因子，有助于细胞周期调节剂的有效剪接。SON 的下调导致纺锤极分离、微管动力学和基因组完整性的严重损伤。这些分子缺陷是由于具有弱剪接位点的特定一组细胞周期相关基因的 RNA 剪接不足所致。此外，我们还表明，SON 促进了 SR 蛋白与 RNA 聚合酶 II 和其他关键剪接体成分的相互作用，这表明它在有效的共转录 RNA 处理中具有功能。这些结果揭示了一种通过 SON 依赖的亚最佳剪接位点的组成性剪接来控制细胞周期进程的机制，这对其在癌症和其他人类疾病中的作用具有重要意义。
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