Dynamic remodelling of human 7SK snRNP controls the nuclear level of active P-TEFb
Dynamic remodelling of human 7SK snRNP controls the nuclear level of active P-TEFb
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DOI：
10.1038/sj.emboj.7601783
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发表时间：
2007-08-08
期刊：
影响因子：
11.4
通讯作者：
Kiss, Tamas
中科院分区：
文献类型：
--
作者：
Van Herreweghe, Elodie;Egloff, Sylvain;Kiss, Tamas
7SK小核RNA（snRNA）通过控制正转录延伸因子B（P-TEF B）的蛋白激酶活性来调节RNA聚合酶II转录延伸。与HEXIM 1合作，7SK snRNA将P-TEFb螯合到激酶失活的7SK/HEXIM 1/P-TEFb小核核糖核蛋白（snRNP）中，从而控制活性P-TEFb的核水平。在这里，我们报告说，HeLa 7SK snRNA的一部分，不参与7SK/HEXIM 1/P-TEFb的形成，特别是与RNA解旋酶A（RHA），异质核核糖核蛋白A1（hnRNP），A2/B1，R和Q蛋白相互作用。细胞转录的抑制诱导7SK/HEXIM 1/P-TEFb的解体，同时增加含有RHA、hnRNP A1、A2/B1、R和Q的7SK snRNP的水平。转录抑制剂的去除恢复了7SK/HEXIM 1/P-TEFb和“7SK/hnRNP”复合物的原始水平。含有缺乏结合hnRNP A1、A2、R和Q能力的突变7SK RNA的7SK/HEXIM 1/P-TEFb snRNP对应激诱导的解体具有抗性，表明新7SK snRNP蛋白的募集对于7SK/HEXIM 1/P-TEFb的破坏是必需的。因此，我们提出，核水平的活性P-TEFb的控制动态和可逆的重塑7SK snRNP。
The 7SK small nuclear RNA (snRNA) regulates RNA polymerase II transcription elongation by controlling the protein kinase activity of the positive transcription elongation factor b ( P-TEFb). In cooperation with HEXIM1, the 7SK snRNA sequesters P-TEFb into the kinase-inactive 7SK/HEXIM1/P-TEFb small nuclear ribonucleoprotein ( snRNP), and thereby, controls the nuclear level of active P-TEFb. Here, we report that a fraction of HeLa 7SK snRNA that is not involved in 7SK/HEXIM1/P-TEFb formation, specifically interacts with RNA helicase A (RHA), heterogeneous nuclear ribonucleoprotein A1 ( hnRNP), A2/B1, R and Q proteins. Inhibition of cellular transcription induces disassembly of 7SK/HEXIM1/P-TEFb and at the same time, increases the level of 7SK snRNPs containing RHA, hnRNP A1, A2/B1, R and Q. Removal of transcription inhibitors restores the original levels of the 7SK/HEXIM1/P-TEFb and '7SK/hnRNP' complexes. 7SK/HEXIM1/P-TEFb snRNPs containing mutant 7SK RNAs lacking the capacity for binding hnRNP A1, A2, R and Q are resistant to stress-induced disassembly, indicating that recruitment of the novel 7SK snRNP proteins is essential for disruption of 7SK/HEXIM1/P-TEFb. Thus, we propose that the nuclear level of active P-TEFb is controlled by dynamic and reversible remodelling of 7SK snRNP.