Yu Ming, Yang Wenjing, Ni Ting, Tang Zhanyun, Nakadai Tomoyoshi, Zhu Jun, Roeder Robert G
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
Systems Biology Center, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
Science. 2015 Dec 11;350(6266):1383-6. doi: 10.1126/science.aad2338.
Release of promoter-proximal paused RNA polymerase II (Pol II) during early elongation is a critical step in transcriptional regulation in metazoan cells. Paused Pol II release is thought to require the kinase activity of cyclin-dependent kinase 9 (CDK9) for the phosphorylation of DRB sensitivity-inducing factor, negative elongation factor, and C-terminal domain (CTD) serine-2 of Pol II. We found that Pol II-associated factor 1 (PAF1) is a critical regulator of paused Pol II release, that positive transcription elongation factor b (P-TEFb) directly regulates the initial recruitment of PAF1 complex (PAF1C) to genes, and that the subsequent recruitment of CDK12 is dependent on PAF1C. These findings reveal cooperativity among P-TEFb, PAF1C, and CDK12 in pausing release and Pol II CTD phosphorylation.
在前体动物细胞中，早期延伸过程中启动子近端暂停的RNA聚合酶II（Pol II）的释放是转录调控中的关键步骤。暂停的Pol II释放被认为需要细胞周期蛋白依赖性激酶9（CDK9）的激酶活性，以磷酸化DRB敏感性诱导因子、负性延伸因子和Pol II的C端结构域（CTD）丝氨酸-2。我们发现，Pol II相关因子1（PAF1）是暂停的Pol II释放的关键调节因子，正性转录延伸因子b（P-TEFb）直接调节PAF1复合物（PAF1C）向基因的初始募集，并且随后CDK12的募集依赖于PAF1C。这些发现揭示了P-TEFb、PAF1C和CDK12在暂停释放和Pol II CTD磷酸化过程中的协同作用。
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