Department of Microbiology and The Center for RNA Biology, The Ohio State University, Columbus, Ohio, USA
Lehrstuhl Biopolymere, Universität Bayreuth, Bayreuth, Germany.
mBio. 2019 Feb 26;10(1):e01547-18. doi: 10.1128/mBio.01547-18.
In every cell from bacteria to mammals, NusG-like proteins bind transcribing RNA polymerase to modulate the rate of nascent RNA synthesis and to coordinate it with numerous cotranscriptional processes that ultimately determine the transcript fate. Housekeeping NusG factors regulate expression of the bulk of the genome, whereas their highly specialized paralogs control just a few targets. In , NusG stimulates silencing of horizontally acquired genes, while its paralog RfaH counters NusG action by activating a subset of these genes. Acting alone or as part of regulatory complexes, NusG factors can promote uninterrupted RNA synthesis, bring about transcription pausing or premature termination, modulate RNA processing, and facilitate translation. Recent structural and mechanistic studies of NusG homologs from all domains of life reveal molecular details of multifaceted interactions that underpin their unexpectedly diverse regulatory roles. NusG proteins share conserved binding sites on RNA polymerase and many effects on the transcription elongation complex but differ in their mechanisms of recruitment, interactions with nucleic acids and secondary partners, and regulatory outcomes. Strikingly, some can alternate between autoinhibited and activated states that possess dramatically different secondary structures to achieve exquisite target specificity.
在从细菌到哺乳动物的所有细胞中，NusG 样蛋白与转录 RNA 聚合酶结合，调节新生 RNA 合成的速度，并与众多转录共发生过程协调，这些过程最终决定了转录本的命运。管家 NusG 因子调节基因组的大部分表达，而其高度特化的同源物仅控制少数几个靶标。在细菌中，NusG 刺激水平获得基因的沉默，而其同源物 RfaH 通过激活这些基因的子集来拮抗 NusG 的作用。NusG 因子单独或作为调控复合物的一部分，可以促进 RNA 合成的不间断进行，引起转录暂停或过早终止，调节 RNA 加工，并促进翻译。来自所有生命领域的 NusG 同源物的最近结构和机制研究揭示了其复杂的相互作用的分子细节，这些相互作用是其出乎意料的多样化调控作用的基础。NusG 蛋白在 RNA 聚合酶上共享保守的结合位点，并对转录延伸复合物产生许多影响，但在募集机制、与核酸和二级伙伴的相互作用以及调控结果方面存在差异。引人注目的是，一些 NusG 蛋白可以在自身抑制和激活状态之间交替，这些状态具有截然不同的二级结构，从而实现极高的靶标特异性。
