Feedback Regulation of Transcriptional Termination by the Mammalian Circadian Clock PERIOD Complex
Feedback Regulation of Transcriptional Termination by the Mammalian Circadian Clock PERIOD Complex
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DOI：
10.1126/science.1221592
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发表时间：
2012-08-03
期刊：
影响因子：
56.9
通讯作者：
Weitz, Charles J.
中科院分区：
文献类型：
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作者：
Padmanabhan, Kiran;Robles, Maria S.;Weitz, Charles J.
真核生物的生物钟是建立在转录反馈环上的。在哺乳动物中，周期蛋白(PER)和隐色素(CRY)蛋白积累，形成一个大的核复合体(PER复合体)，并抑制自身的转录。我们发现小鼠PER复合体包括RNA解旋酶DDX5和DHX9，活性RNA聚合酶II大亚基，PER和Cry前-mRNAs，以及促进转录终止的解旋酶SETX。在昼夜节律负反馈期间，RNA聚合酶II在PER和Cry基因的末端附近积累，而在对照基因上不积累。PER复合体在PER和Cry末端的延伸聚合酶上的募集抑制了SETX的作用，阻碍了RNA聚合酶II的释放，从而抑制了转录的重新启动。因此，生物钟负反馈包括对转录终止的直接控制。
Eukaryotic circadian clocks are built on transcriptional feedback loops. In mammals, the PERIOD (PER) and CRYPTOCHROME (CRY) proteins accumulate, form a large nuclear complex (PER complex), and repress their own transcription. We found that mouse PER complexes included RNA helicases DDX5 and DHX9, active RNA polymerase II large subunit, Per and Cry pre-mRNAs, and SETX, a helicase that promotes transcriptional termination. During circadian negative feedback, RNA polymerase II accumulated near termination sites on Per and Cry genes but not on control genes. Recruitment of PER complexes to the elongating polymerase at Per and Cry termination sites inhibited SETX action, impeding RNA polymerase II release and thereby repressing transcriptional reinitiation. Circadian clock negative feedback thus includes direct control of transcriptional termination.