CDK9 and PPA2 regulate the link between RNA polymerase II transcription termination and RNA maturation
CDK9 and PPA2 regulate the link between RNA polymerase II transcription termination and RNA maturation
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CDK9 和 PPA2 调节 RNA 聚合酶 II 转录终止和 RNA 成熟之间的联系
DOI：
10.1101/2021.06.21.449289
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
and Murphy S
中科院分区：
文献类型：
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作者：
1.Tellier M;Zaborowska J;Neve J;Nojima T;Hester S;Furger A;and Murphy S
CDK 9是一种对RNA聚合酶II（pol II）的蛋白编码基因的生产性转录至关重要的激酶。作为P-TEFb的一部分，CDK 9磷酸化pol II和延伸因子的羧基末端结构域（CTD），这使得pol II能够延伸超过启动后不久遇到的早期延伸检查点（EEC）。我们发现，除了停止pol II在EEC，CDK 9活性的损失会导致转录提前终止的最后一个外显子，从染色质的聚腺苷酸化因子的损失，和新生的成绩单的聚腺苷酸化的损失。磷酸酶PP 2A的抑制消除了由CDK 9抑制引起的多聚腺苷酸化的过早终止和丧失，表明这种激酶/磷酸酶对调节蛋白质编码基因末端的转录延伸和RNA加工。我们还确认了剪接因子SF 3B 1作为CDK 9的靶点，并表明在CDK 9抑制后，与多聚腺苷酸化因子复合的SF 3B 1从染色质中丢失。这些结果强调了CDK 9在将转录延伸和终止与EEC下游的RNA成熟偶联中发挥的重要作用。
CDK9 is a kinase critical for the productive transcription of protein‐coding genes by RNA polymerase II (pol II). As part of P‐TEFb, CDK9 phosphorylates the carboxyl‐terminal domain (CTD) of pol II and elongation factors, which allows pol II to elongate past the early elongation checkpoint (EEC) encountered soon after initiation. We show that, in addition to halting pol II at the EEC, loss of CDK9 activity causes premature termination of transcription across the last exon, loss of polyadenylation factors from chromatin, and loss of polyadenylation of nascent transcripts. Inhibition of the phosphatase PP2A abrogates the premature termination and loss of polyadenylation caused by CDK9 inhibition, indicating that this kinase/phosphatase pair regulates transcription elongation and RNA processing at the end of protein‐coding genes. We also confirm the splicing factor SF3B1 as a target of CDK9 and show that SF3B1 in complex with polyadenylation factors is lost from chromatin after CDK9 inhibition. These results emphasize the important roles that CDK9 plays in coupling transcription elongation and termination to RNA maturation downstream of the EEC.