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The PNUTS phosphatase complex controls transcription pause release
Molecular Cell ( IF 14.5 ) Pub Date : 2024-11-26 , DOI: 10.1016/j.molcel.2024.10.045 Jessica R. Kelley, Emilia Dimitrova, Maciej Maciuszek, Hieu T. Nguyen, Aleksander T. Szczurek, Amy L. Hughes, Neil P. Blackledge, Arminja N. Kettenbach, Robert J. Klose
Molecular Cell ( IF 14.5 ) Pub Date : 2024-11-26 , DOI: 10.1016/j.molcel.2024.10.045 Jessica R. Kelley, Emilia Dimitrova, Maciej Maciuszek, Hieu T. Nguyen, Aleksander T. Szczurek, Amy L. Hughes, Neil P. Blackledge, Arminja N. Kettenbach, Robert J. Klose
Gene expression is regulated by controlling distinct steps of the transcriptional cycle, including initiation, pausing, elongation, and termination. Kinases phosphorylate RNA polymerase II (RNA Pol II) and associated factors to control transitions between these steps and to act as central gene regulatory nodes. Similarly, phosphatases that dephosphorylate these components are emerging as important regulators of transcription, although their roles remain less well understood. Here, we discover that the mouse PNUTS-PP1 phosphatase complex plays an essential role in controlling transcription pause release in addition to its previously described function in transcription termination. Transcription pause release by the PNUTS complex is essential for almost all RNA Pol II-dependent gene transcription, relies on its PP1 phosphatase subunit, and controls the phosphorylation of factors required for pause release and elongation. Together, these observations reveal an essential new role for a phosphatase complex in transcription pause release and show that the PNUTS complex is essential for RNA Pol II-dependent transcription.
中文翻译:
PNUTS 磷酸酶复合物控制转录暂停释放
基因表达通过控制转录周期的不同步骤(包括起始、暂停、延伸和终止)来调节。激酶磷酸化 RNA 聚合酶 II (RNA Pol II) 和相关因子,以控制这些步骤之间的转换,并充当中心基因调控节点。同样,使这些成分去磷酸化的磷酸酶正在成为重要的转录调节因子,尽管它们的作用仍不太清楚。在这里,我们发现小鼠 PNUTS-PP1 磷酸酶复合物除了在先前描述的转录终止功能外,还在控制转录暂停释放中起着重要作用。PNUTS 复合物的转录暂停释放对于几乎所有 RNA Pol II 依赖性基因转录都是必不可少的,依赖于其 PP1 磷酸酶亚基,并控制暂停释放和延伸所需因子的磷酸化。总之,这些观察结果揭示了磷酸酶复合物在转录暂停释放中的重要新作用,并表明 PNUTS 复合物对于 RNA Pol II 依赖性转录至关重要。
更新日期:2024-11-26
中文翻译:
PNUTS 磷酸酶复合物控制转录暂停释放
基因表达通过控制转录周期的不同步骤(包括起始、暂停、延伸和终止)来调节。激酶磷酸化 RNA 聚合酶 II (RNA Pol II) 和相关因子,以控制这些步骤之间的转换,并充当中心基因调控节点。同样,使这些成分去磷酸化的磷酸酶正在成为重要的转录调节因子,尽管它们的作用仍不太清楚。在这里,我们发现小鼠 PNUTS-PP1 磷酸酶复合物除了在先前描述的转录终止功能外,还在控制转录暂停释放中起着重要作用。PNUTS 复合物的转录暂停释放对于几乎所有 RNA Pol II 依赖性基因转录都是必不可少的,依赖于其 PP1 磷酸酶亚基,并控制暂停释放和延伸所需因子的磷酸化。总之,这些观察结果揭示了磷酸酶复合物在转录暂停释放中的重要新作用,并表明 PNUTS 复合物对于 RNA Pol II 依赖性转录至关重要。