Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada.
Nucleic Acids Res. 2020 Sep 18;48(16):9285-9300. doi: 10.1093/nar/gkaa675.
The genomes of RNA viruses contain regulatory elements of varying complexity. Many plus-strand RNA viruses employ largescale intra-genomic RNA-RNA interactions as a means to control viral processes. Here, we describe an elaborate RNA structure formed by multiple distant regions in a tombusvirus genome that activates transcription of a viral subgenomic mRNA. The initial step in assembly of this intramolecular RNA complex involves the folding of a large viral RNA domain, which generates a discontinuous binding pocket. Next, a distally-located protracted stem-loop RNA structure docks, via base-pairing, into the binding site and acts as a linchpin that stabilizes the RNA complex and activates transcription. A multi-step RNA folding pathway is proposed in which rate-limiting steps contribute to a delay in transcription of the capsid protein-encoding viral subgenomic mRNA. This study provides an exceptional example of the complexity of genome-scale viral regulation and offers new insights into the assembly schemes utilized by large intra-genomic RNA structures.
RNA 病毒的基因组包含具有不同复杂性的调节元件。许多正链 RNA 病毒利用大规模的基因组内 RNA-RNA 相互作用作为控制病毒过程的一种手段。在这里，我们描述了一种由弹状病毒基因组中多个远距离区域形成的精细 RNA 结构，该结构激活病毒亚基因组 mRNA 的转录。这种分子内 RNA 复合物组装的初始步骤涉及到一个大的病毒 RNA 结构域的折叠，该结构域产生一个不连续的结合口袋。接下来，一个位于远端的延长茎环 RNA 结构通过碱基配对对接进入结合位点，并作为稳定 RNA 复合物和激活转录的关键。提出了一种多步 RNA 折叠途径，其中限速步骤导致衣壳蛋白编码病毒亚基因组 mRNA 的转录延迟。这项研究提供了一个关于基因组规模病毒调节复杂性的特殊例子，并为利用大型基因组内 RNA 结构的组装方案提供了新的见解。
