Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada.
Nucleic Acids Res. 2023 Sep 8;51(16):8787-8804. doi: 10.1093/nar/gkad550.
Many eukaryotic RNA viruses transcribe subgenomic (sg) mRNAs during infections to control expression of a subset of viral genes. Such transcriptional events are commonly regulated by local or long-range intragenomic interactions that form higher-order RNA structures within these viral genomes. In contrast, here we report that an umbravirus activates sg mRNA transcription via base pair-mediated dimerization of its plus-strand RNA genome. Compelling in vivo and in vitro evidence demonstrate that this viral genome dimerizes via a kissing-loop interaction involving an RNA stem-loop structure located just upstream from its transcriptional initiation site. Both specific and non-specific features of the palindromic kissing-loop complex were found to contribute to transcriptional activation. Structural and mechanistic aspects of the process in umbraviruses are discussed and compared with genome dimerization events in other RNA viruses. Notably, probable dimer-promoting RNA stem-loop structures were also identified in a diverse group of umbra-like viruses, suggesting broader utilization of this unconventional transcriptional strategy.
许多真核 RNA 病毒在感染过程中会转录亚基因组 (sg) mRNA,以控制一部分病毒基因的表达。这些转录事件通常受到局部或长距离的基因组内相互作用的调控,这些相互作用在这些病毒基因组内形成了更高阶的 RNA 结构。相比之下,在这里我们报告说,一种 Umbravirus 通过其正链 RNA 基因组的碱基配对介导二聚化来激活 sg mRNA 转录。令人信服的体内和体外证据表明,这种病毒基因组通过涉及位于转录起始位点上游的 RNA 茎环结构的“亲吻环”相互作用进行二聚化。发现发夹环复合物的特异性和非特异性特征都有助于转录激活。讨论了 Umbraviruses 中该过程的结构和机制方面,并与其他 RNA 病毒中的基因组二聚化事件进行了比较。值得注意的是,在一组不同的 Umbra-like 病毒中也鉴定出了可能促进二聚化的 RNA 茎环结构,这表明这种非常规的转录策略得到了更广泛的利用。