CDK12 globally stimulates RNA polymerase II transcription elongation and carboxyl-terminal domain phosphorylation.
CDK12 globally stimulates RNA polymerase II transcription elongation and carboxyl-terminal domain phosphorylation.
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DOI：
10.1093/nar/gkaa514
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发表时间：
2020-08-20
影响因子：
14.9
通讯作者：
Murphy S
中科院分区：
文献类型：
--
作者：
Tellier M;Zaborowska J;Caizzi L;Mohammad E;Velychko T;Schwalb B;Ferrer-Vicens I;Blears D;Nojima T;Cramer P;Murphy S
细胞周期蛋白依赖性激酶12 （CDK12）磷酸化RNA聚合酶II （pol II）的羧基末端结构域（CTD），但其在DNA损伤反应基因表达以外的转录中的作用尚不清楚。在这里，我们使用TT-seq和mNET-seq来监测快速抑制CDK12对人类细胞转录活性和CTD磷酸化的直接影响。CDK12抑制导致转录延伸的全基因组缺陷和CTD Ser2和Ser5磷酸化的全局减少。伸长率缺陷的原因是新伸长化的pol II失去了伸长率因子LEO1和CDC73、部分PAF1复合物和SPT6。我们的研究结果表明，CDK12是pol II转录延伸的一般激活剂，并且表明它靶向pol II CTD的Ser2和Ser5残基。
Cyclin-dependent kinase 12 (CDK12) phosphorylates the carboxyl-terminal domain (CTD) of RNA polymerase II (pol II) but its roles in transcription beyond the expression of DNA damage response genes remain unclear. Here, we have used TT-seq and mNET-seq to monitor the direct effects of rapid CDK12 inhibition on transcription activity and CTD phosphorylation in human cells. CDK12 inhibition causes a genome-wide defect in transcription elongation and a global reduction of CTD Ser2 and Ser5 phosphorylation. The elongation defect is explained by the loss of the elongation factors LEO1 and CDC73, part of PAF1 complex, and SPT6 from the newly-elongating pol II. Our results indicate that CDK12 is a general activator of pol II transcription elongation and indicate that it targets both Ser2 and Ser5 residues of the pol II CTD.