7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes
7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes
复制标题
DOI：
10.1038/35104581
复制
发表时间：
2001-11-15
期刊：
影响因子：
64.8
通讯作者：
Bensaude, O
中科院分区：
文献类型：
--
作者：
Nguyen, VT;Kiss, TS;Bensaude, O
真核生物蛋白质编码基因的转录涉及对RNA聚合酶（Pol）II活性的复杂调控，以响应生理条件和发育信号。这种调控的一个要素是由转录延伸因子P - TEFb对最大聚合酶亚基的羧基末端结构域（CTD）进行磷酸化，P - TEFb由激酶CDK9和细胞周期蛋白T1或T2组成（参考文献1）。在此我们报道，在人类HeLa细胞中，超过一半的P - TEFb被隔离在更大的复合物中，这些复合物还含有7SK RNA，这是一种大量存在的、功能迄今未知的小核RNA（snRNA）（2,3）。P - TEFb和7SK以一种特定且可逆的方式结合。与具有高激酶活性的较小的P - TEFb复合物不同，较大的7SK/P - TEFb复合物显示出非常弱的激酶活性。化学试剂或紫外线照射对细胞转录的抑制会引发P - TEFb/7SK复合物的完全解离，并增强CDK9的活性。因此，P - TEFb与7SK的转录依赖性相互作用可能有助于形成一个重要的反馈回路，调节RNA Pol II的活性。
The transcription of eukaryotic protein-coding genes involves complex regulation of RNA polymerase (Pol) II activity in response to physiological conditions and developmental cues. One element of this regulation involves phosphorylation of the carboxy-terminal domain (CTD) of the largest polymerase subunit by a transcription elongation factor, P-TEFb, which comprises the kinase CDK9 and cyclin T1 or T2 (ref. 1). Here we report that in human HeLa cells more than half of the P-TEFb is sequestered in larger complexes that also contain 7SK RNA, an abundant, small nuclear RNA (snRNA) of hitherto unknown function(2,3). P-TEFb and 7SK associate in a specific and reversible manner. In contrast to the smaller P-TEFb complexes, which have a high kinase activity, the larger 7SK/P-TEFb complexes show very weak kinase activity. Inhibition of cellular transcription by chemical agents or ultraviolet irradiation trigger the complete disruption of the P-TEFb/7SK complex, and enhance CDK9 activity. The transcription-dependent interaction of P-TEFb with 7SK may therefore contribute to an important feedback loop modulating the activity of RNA Pol II.