Department of Molecular, Cell and Developmental Biology and Center for Molecular Biology of RNA, University of California Santa Cruz, Santa Cruz, CA, USA.
Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA.
Sci Rep. 2022 Dec 15;12(1):21694. doi: 10.1038/s41598-022-26135-9.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19) in humans, with symptoms ranging from mild to severe, including fatality. The molecular mechanisms surrounding the effects of viral infection on the host RNA machinery remain poorly characterized. We used a comparative transcriptomics approach to investigate the effects of SARS-CoV-2 infection on the host mRNA and sRNA expression machinery in a human lung epithelial cell line (Calu-3) and an African green monkey kidney cell line (Vero-E6). Upon infection, we observed global changes in host gene expression and differential expression of dozens of host miRNAs, many with known links to viral infection and immune response. Additionally, we discovered an expanded landscape of more than a hundred SARS-CoV-2-derived small viral RNAs (svRNAs) predicted to interact with differentially expressed host mRNAs and miRNAs. svRNAs are derived from distinct regions of the viral genome and sequence signatures suggest they are produced by a non-canonical biogenesis pathway. 52 of the 67 svRNAs identified in Calu-3 cells are predicted to interact with differentially expressed miRNAs, with many svRNAs having multiple targets. Accordingly, we speculate that these svRNAs may play a role in SARS-CoV-2 propagation by modulating post-transcriptional gene regulation, and that methods for antagonizing them may have therapeutic value.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）在人类中引起冠状病毒病（COVID-19），症状从轻度到重度不等，包括死亡。病毒感染对宿主 RNA 机制的影响的分子机制仍未得到很好的描述。我们使用比较转录组学方法来研究 SARS-CoV-2 感染对人肺上皮细胞系（Calu-3）和非洲绿猴肾细胞系（Vero-E6）中宿主 mRNA 和 sRNA 表达机制的影响。感染后，我们观察到宿主基因表达的全局变化和数十种宿主 miRNA 的差异表达，其中许多与病毒感染和免疫反应有关。此外，我们发现了一个由一百多个 SARS-CoV-2 衍生的小病毒 RNA（svRNA）组成的扩展景观，这些 RNA 被预测与差异表达的宿主 mRNA 和 miRNA 相互作用。svRNA 来源于病毒基因组的不同区域，序列特征表明它们是通过非典型的生物发生途径产生的。在 Calu-3 细胞中鉴定的 67 个 svRNA 中有 52 个被预测与差异表达的 miRNA 相互作用，许多 svRNA 具有多个靶标。因此，我们推测这些 svRNA 可能通过调节转录后基因调控在 SARS-CoV-2 的增殖中发挥作用，并且拮抗它们的方法可能具有治疗价值。
