Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejon 34141, Republic of Korea.
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
J Mol Biol. 2019 Sep 20;431(20):4007-4029. doi: 10.1016/j.jmb.2019.07.017. Epub 2019 Jul 13.
Pausing by RNA polymerase (RNAP) during transcription regulates gene expression in all domains of life. In this review, we recap the history of transcriptional pausing discovery, summarize advances in our understanding of the underlying causes of pausing since then, and describe new insights into the pausing mechanisms and pause modulation by transcription factors gained from structural and biochemical experiments. The accumulated evidence to date suggests that upon encountering a pause signal in the nucleic-acid sequence being transcribed, RNAP rearranges into an elemental, catalytically inactive conformer unable to load NTP substrate. The conformation, and as a consequence lifetime, of an elemental paused RNAP is modulated by backtracking, nascent RNA structure, binding of transcription regulators, or a combination of these mechanisms. We conclude the review by outlining open questions and directions for future research in the field of transcriptional pausing.
在转录过程中暂停 RNA 聚合酶（RNAP）可调节所有生命领域的基因表达。在这篇综述中，我们回顾了转录暂停发现的历史，总结了自那时以来对暂停潜在原因的理解的进展，并描述了结构和生化实验获得的有关转录因子通过暂停机制和暂停调节的新见解。迄今为止，累积的证据表明，当在被转录的核酸序列中遇到暂停信号时，RNAP 会重新排列成基本的、无催化活性的构象，无法加载 NTP 底物。基本暂停 RNAP 的构象，以及因此的寿命，可通过回溯、新生 RNA 结构、转录调节剂的结合或这些机制的组合来调节。我们通过概述转录暂停领域的开放性问题和未来研究方向来结束综述。
