近日，美国斯坦福大学Christine Jacobs-Wagner和耶鲁大学Sangjin Kim等研究人员合作发现，通过DNA超螺旋实现远程协同和拮抗RNA聚合酶（RNAP）动态。这一研究成果于2019年9月19日发表在《细胞》上。

研究人员发现一个内置机制的体外和体内证据，通过该机制，共转录RNAP通过转录引起的DNA超螺旋表现出长距离（> 2kb）的协同或拮抗动态。在大肠杆菌中，当启动子具有活性时，共转录RNA的转运速度比单个RNAP快，但它们的平均速度不会因启动子强度和RNAP密度的大的变化而改变。环境引起的启动子抑制降低了已经加载的RNAP的延伸效率，导致过早终止和不再需要的蛋白质的快速合成停滞。这种负面影响似乎与RNAP队列形成无关，并且被拓扑异构酶I活性消除。在来自不同转录的基因对的RNAP之间也可发生拮抗动态。这些研究结果可能广泛适用，因为拓扑受限DNA上的转录是不同生物钟普遍存在的。

据介绍，基因通常由多种RNAP转录，其密度可在基因和环境条件之间变化很大。

附：英文原文

Title: Long-Distance Cooperative and Antagonistic RNA Polymerase Dynamics via DNA Supercoiling

Author: Sangjin Kim, Bruno Beltran, Irnov Irnov, Christine Jacobs-Wagner

Issue&Volume: Volume 179 Issue 1

Abstract: Genes are often transcribed by multiple RNA polymerases (RNAPs) at densities that can vary widely across genes and environmental conditions. Here, we provide in vitro and in vivo evidence for a built-in mechanism by which co-transcribing RNAPs display either collaborative or antagonistic dynamics over long distances (>2 kb) through transcription-induced DNA supercoiling. In Escherichia coli, when the promoter is active, co-transcribing RNAPs translocate faster than a single RNAP, but their average speed is not altered by large variations in promoter strength and thus RNAP density. Environmentally induced promoter repression reduces the elongation efficiency of already-loaded RNAPs, causing premature termination and quick synthesis arrest of no-longer-needed proteins. This negative effect appears independent of RNAP convoy formation and is abrogated by topoisomerase I activity. Antagonistic dynamics can also occur between RNAPs from divergently transcribed gene pairs. Our findings may be broadly applicable given that transcription on topologically constrained DNA is the norm across organisms.

DOI: 10.1016/j.cell.2019.08.033

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30952-3