Grelewska-Nowotko Katarzyna, Elhag Ahmed Eisa, Turowski Tomasz Wojciech
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Department of Preventive Medicine and Clinical Studies, Faculty of Veterinary Sciences, University of Gadarif, Al Qadarif, Sudan.
Wiley Interdiscip Rev RNA. 2025 Jan-Feb;16(1):e70000. doi: 10.1002/wrna.70000.
Coronaviruses utilize a positive-sense single-strand RNA, functioning simultaneously as mRNA and the genome. An RNA-dependent RNA polymerase (RdRP) plays a dual role in transcribing genes and replicating the genome, making RdRP a critical target in therapies against coronaviruses. This review explores recent advancements in understanding the coronavirus transcription machinery, discusses it within virus infection context, and incorporates kinetic considerations on RdRP activity. We also address steric limitations in coronavirus replication, particularly during early infection phases, and outline hypothesis regarding translation-transcription conflicts, postulating the existence of mechanisms that resolve these issues. In cells infected by coronaviruses, abundant structural proteins are synthesized from subgenomic RNA fragments (sgRNAs) produced via discontinuous transcription. During elongation, RdRP can skip large sections of the viral genome, resulting in the creation of shorter sgRNAs that reflects the stoichiometry of viral structural proteins. Although the precise mechanism of discontinuous transcription remains unknown, we discuss recent hypotheses involving long-distance RNA-RNA interactions, helicase-mediated RdRP backtracking, dissociation and reassociation of RdRP, and RdRP dimerization.
冠状病毒利用正链单链RNA，其同时作为信使核糖核酸（mRNA）和基因组发挥作用。RNA依赖性RNA聚合酶（RdRP）在基因转录和基因组复制中起双重作用，这使得RdRP成为抗冠状病毒疗法的关键靶点。本综述探讨了在理解冠状病毒转录机制方面的最新进展，在病毒感染背景下对其进行了讨论，并纳入了关于RdRP活性的动力学考量。我们还阐述了冠状病毒复制过程中的空间限制，特别是在早期感染阶段，并概述了关于翻译-转录冲突的假说，推测存在解决这些问题的机制。在被冠状病毒感染的细胞中，丰富的结构蛋白由通过不连续转录产生的亚基因组RNA片段（sgRNA）合成。在延伸过程中，RdRP可以跳过病毒基因组的大部分区域，从而产生较短的sgRNA，其反映了病毒结构蛋白的化学计量。尽管不连续转录的确切机制仍然未知，但我们讨论了最近的假说，这些假说涉及长距离RNA-RNA相互作用、解旋酶介导的RdRP回溯、RdRP的解离和重新结合以及RdRP二聚化。
