德国柏林自由大学Markus C. Wahl、美国俄亥俄州立大学Irina Artsimovitch研究组合作取得最新进展。他们揭示通过终止子ATPase ρ进行不依赖于转运的RNA聚合酶失活的步骤。该项研究成果发表在2020年11月26日出版的《科学》杂志上。

他们确定了一系列的冷冻电镜结构，描绘了终止NusA / NusG修饰的延伸复合物的路径上的六聚ATPase ρ。一个开放的ρ环接触NusA、NusG和RNA聚合酶的多个区域，捕获并局部打开近端上游DNA。NusA楔入ρ环，最初隔离RNA。在RNA聚合酶Zinc结合结构域上方偏转远端上游DNA后，NusA在一个加帽ρ亚基下方旋转，随后捕获RNA。

在NusG脱离捕获释放后，RNA聚合酶失去了对RNA：DNA杂合体的控制并被灭活。他们的结构和功能分析表明，整个生命周期中的ρ和其他终止因子可能利用类似的策略以构象方式捕获处于垂死状态的转录复合物。

研究人员表示，依赖因子的转录终止机制了解甚少。

附：英文原文

Title: Steps toward translocation-independent RNA polymerase inactivation by terminator ATPase ρ

Author: Nelly Said, Tarek Hilal, Nicholas D. Sunday, Ajay Khatri, Jrg Bürger, Thorsten Mielke, Georgiy A. Belogurov, Bernhard Loll, Ranjan Sen, Irina Artsimovitch, Markus C. Wahl

Issue&Volume: 2020/11/26

Abstract: Factor-dependent transcription termination mechanisms are poorly understood. We determined a series of cryo-electron microscopy structures portraying the hexameric ATPase ρ on path to terminating NusA/NusG-modified elongation complexes. An open ρ ring contacts NusA, NusG, and multiple regions of RNA polymerase, trapping and locally unwinding proximal upstream DNA. NusA wedges into the ρ ring, initially sequestering RNA. Upon deflection of distal upstream DNA over the RNA polymerase Zinc-binding domain, NusA rotates underneath one capping ρ subunit, which subsequently captures RNA. Following detachment of NusG and clamp opening, RNA polymerase loses its grip on the RNA:DNA hybrid and is inactivated. Our structural and functional analyses suggest that ρ and other termination factors across life may utilize analogous strategies to allosterically trap transcription complexes in a moribund state.

DOI: 10.1126/science.abd1673

Source: https://science.sciencemag.org/content/early/2020/11/24/science.abd1673