Qian Jin, Xu Wenxuan, Dunlap David, Finzi Laura
Emory University, Atlanta, GA, USA.
Transcription. 2021 Aug;12(4):219-231. doi: 10.1080/21541264.2021.1997315. Epub 2021 Nov 1.
During transcription, RNA polymerase (RNAP) translocates along the helical template DNA while maintaining high transcriptional fidelity. However, all genomes are dynamically twisted, writhed, and decorated by bound proteins and motor enzymes. In prokaryotes, proteins bound to DNA, specifically or not, frequently compact DNA into conformations that may silence genes by obstructing RNAP. Collision of RNAPs with these architectural proteins, may result in RNAP stalling and/or displacement of the protein roadblock. It is important to understand how rapidly transcribing RNAPs operate under different levels of supercoiling or in the presence of roadblocks. Given the broad range of asynchronous dynamics exhibited by transcriptional complexes, single-molecule assays, such as atomic force microscopy, fluorescence detection, optical and magnetic tweezers, etc. are well suited for detecting and quantifying activity with adequate spatial and temporal resolution. Here, we summarize current understanding of the effects of torsion and roadblocks on prokaryotic transcription, with a focus on single-molecule assays that provide real-time detection and readout.
在转录过程中,RNA聚合酶(RNAP)沿着螺旋形模板DNA移动,同时保持高转录保真度。然而,所有基因组都会因结合的蛋白质和运动酶而动态扭曲、缠绕并修饰。在原核生物中,与DNA特异性或非特异性结合的蛋白质经常将DNA压缩成可能通过阻碍RNAP使基因沉默的构象。RNAP与这些结构蛋白的碰撞可能导致RNAP停滞和/或蛋白质障碍的移位。了解快速转录的RNAP在不同超螺旋水平或存在障碍的情况下如何运作非常重要。鉴于转录复合物表现出广泛的异步动力学,单分子检测方法,如原子力显微镜、荧光检测、光学和磁性镊子等,非常适合以足够的空间和时间分辨率检测和量化活性。在这里,我们总结了目前对扭转和障碍对原核生物转录影响的理解,重点是提供实时检测和读数的单分子检测方法。