Mycobacterial HelD is a nucleic acids-clearing factor for RNA polymerase.
Mycobacterial HelD is a nucleic acids-clearing factor for RNA polymerase.
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DOI：
10.1038/s41467-020-20158-4
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发表时间：
2020-12-18
影响因子：
16.6
通讯作者：
Krásný L
中科院分区：
文献类型：
--
作者：
Kouba T;Koval' T;Sudzinová P;Pospíšil J;Brezovská B;Hnilicová J;Šanderová H;Janoušková M;Šiková M;Halada P;Sýkora M;Barvík I;Nováček J;Trundová M;Dušková J;Skálová T;Chon U;Murakami KS;Dohnálek J;Krásný L
RNA合成是生命的核心，RNA聚合酶（RNAP）依赖于辅助因子从停滞状态中恢复并适应环境变化。在这里，我们研究了解旋酶样因子HelD循环RNAP的机制。我们报告了耻垢分枝杆菌RNAP和HelD之间复合物的低温电镜结构。月牙形的HelD同时深入到负责核酸结合和底物递送到活性位点的两个RNAP通道中，从而将RNAP锁定在非活性状态。我们发现，HelD阻止RNAP和DNA之间的非特异性相互作用，并解离停滞的转录延伸复合物。释放的RNAP可以保持休眠状态，被HelD隔离，或者在HelD释放后重新开始转录。我们的研究结果提供了对与医学高度相关的分枝杆菌转录机制的结构和调控的见解，并将HelD定义为一种清除因子，可将RNAP从与核酸的无功能复合物中释放出来。细菌解旋酶样转录因子HelD与RNA聚合酶（RNAP）结合并循环停滞的转录复合物。在这里，作者展示了三种耻垢分枝杆菌hold结合RNAP复合物的低温电镜结构，并进一步表明hold可以阻止RNAP核心与非特异性DNA的结合，并主动从停滞的延伸复合物中去除RNAP。
RNA synthesis is central to life, and RNA polymerase (RNAP) depends on accessory factors for recovery from stalled states and adaptation to environmental changes. Here, we investigated the mechanism by which a helicase-like factor HelD recycles RNAP. We report a cryo-EM structure of a complex between the Mycobacterium smegmatis RNAP and HelD. The crescent-shaped HelD simultaneously penetrates deep into two RNAP channels that are responsible for nucleic acids binding and substrate delivery to the active site, thereby locking RNAP in an inactive state. We show that HelD prevents non-specific interactions between RNAP and DNA and dissociates stalled transcription elongation complexes. The liberated RNAP can either stay dormant, sequestered by HelD, or upon HelD release, restart transcription. Our results provide insights into the architecture and regulation of the highly medically-relevant mycobacterial transcription machinery and define HelD as a clearing factor that releases RNAP from nonfunctional complexes with nucleic acids. The bacterial helicase-like transcription factor HelD associates with the RNA polymerase (RNAP) and recycles stalled transcription complexes. Here, the authors present the cryo-EM structures of three Mycobacterium smegmatis HelD bound RNAP complexes and further show that HelD can prevent the binding of the RNAP core to non-specific DNA and also actively removes RNAP from stalled elongation complexes.
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影响因子：
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DOI：
10.1107/s0907444904019158
发表时间：
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