The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription
The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription
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DOI：
10.1038/35104575
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发表时间：
2001-11-15
期刊：
影响因子：
64.8
通讯作者：
Zhou, Q
中科院分区：
文献类型：
--
作者：
Yang, ZY;Zhu, QW;Zhou, Q
人类正转录延伸因子P - TEFb由CDK9/细胞周期蛋白T1异二聚体组成，既是一种通用的转录因子，也是一种HIV - 1 Tat特异性转录因子（1,2）。P - TEFb通过使RNA聚合酶（Pol）II磷酸化来激活转录，从而导致持续延伸复合物的形成。作为Tat辅因子，P - TEFb通过与Tat以及位于新生病毒转录本5'端的反式激活应答（TAR）RNA结构相互作用来刺激HIV - 1转录（3）。在此我们鉴定出7SK，一种功能未知的大量且在进化上保守的小核RNA（snRNA）（4,5），它是一种与P - TEFb相关的特异性因子。7SK通过抑制CDK9的激酶活性以及阻止P - TEFb募集到HIV - 1启动子，在体内和体外抑制P - TEFb的通用转录活性和HIV - 1 Tat特异性转录活性。通过用紫外线照射和放线菌素D处理细胞，7SK可有效地从P - TEFb上解离下来。由于这两种试剂已被证明可显著增强HIV - 1转录以及Pol II的磷酸化（参考文献6 - 8），我们的数据为它们的刺激作用提供了一种机制上的解释。7SK/P - TEFb相互作用可能作为应激相关反应期间细胞和HIV - 1病毒基因表达诱导的一个主要控制点。我们的研究证明了一种snRNA参与控制一种Cdk - 细胞周期蛋白激酶的活性。
The human positive transcription elongation factor P-TEFb, consisting of a CDK9/cyclin T1 heterodimer, functions as both a general and an HIV-1 Tat-specific transcription factor(1,2). P-TEFb activates transcription by phosphorylating RNA polymerase (Pol) II, leading to the formation of processive elongation complexes. As a Tat cofactor, P-TEFb stimulates HIV-1 transcription by interacting with Tat and the transactivating responsive (TAR) RNA structure located at the 5' end of the nascent viral transcript(3). Here we identified 7SK, an abundant and evolutionarily conserved small nuclear RNA (snRNA) of unknown function(4,5), as a specific P-TEFb-associated factor. 7SK inhibits general and HIV-1 Tat-specific transcriptional activities of P-TEFb in vivo and in vitro by inhibiting the kinase activity of CDK9 and preventing recruitment of P-TEFb to the HIV-1 promoter. 7SK is efficiently dissociated from P-TEFb by treatment of cells with ultraviolet irradiation and actinomycin D. As these two agents have been shown to significantly enhance HIV-1 transcription and phosphorylation of Pol II (refs 6-8), our data provide a mechanistic explanation for their stimulatory effects. The 7SK/P-TEFb interaction may serve as a principal control point for the induction of cellular and HIV-1 viral gene expression during stress-related responses. Our studies demonstrate the involvement of an snRNA in controlling the activity of a Cdk-cyclin kinase.