National Institute of Biomedical Genomics, Kalyani, West Bengal, India.
PLoS One. 2020 Aug 11;15(8):e0237559. doi: 10.1371/journal.pone.0237559. eCollection 2020.
The world is going through the critical phase of COVID-19 pandemic, caused by human coronavirus, SARS-CoV-2. Worldwide concerted effort to identify viral genomic changes across different sub-types has identified several strong changes in the coding region. However, there have not been many studies focusing on the variations in the 5' and 3' untranslated regions and their consequences. Considering the possible importance of these regions in host mediated regulation of viral RNA genome, we wanted to explore the phenomenon.
To have an idea of the global changes in 5' and 3'-UTR sequences, we downloaded 8595 complete and high-coverage SARS-CoV-2 genome sequence information from human host in FASTA format from Global Initiative on Sharing All Influenza Data (GISAID) from 15 different geographical regions. Next, we aligned them using Clustal Omega software and investigated the UTR variants. We also looked at the putative host RNA binding protein (RBP) and microRNA binding sites in these regions by 'RBPmap' and 'RNA22 v2' respectively. Expression status of selected RBPs and microRNAs were checked in lungs tissue.
We identified 28 unique variants in SARS-CoV-2 UTR region based on a minimum variant percentage cut-off of 0.5. Along with 241C>T change the important 5'-UTR change identified was 187A>G, while 29734G>C, 29742G>A/T and 29774C>T were the most familiar variants of 3'UTR among most of the continents. Furthermore, we found that despite the variations in the UTR regions, binding of host RBP to them remains mostly unaltered, which further influenced the functioning of specific miRNAs.
Our results, shows for the first time in SARS-Cov-2 infection, a possible cross-talk between host RBPs-miRNAs and viral UTR variants, which ultimately could explain the mechanism of escaping host RNA decay machinery by the virus. The knowledge might be helpful in developing anti-viral compounds in future.
世界正处于由人类冠状病毒 SARS-CoV-2 引起的 COVID-19 大流行的关键阶段。全球齐心协力地在不同亚型中识别病毒基因组变化，已在编码区中发现了几个强烈的变化。然而，针对 5'和 3'非翻译区及其后果的变异，并没有太多的研究。考虑到这些区域在宿主介导的病毒 RNA 基因组调控中可能具有重要性，我们希望探索这一现象。
为了了解 5'和 3'-UTR 序列的全球变化，我们从全球流感共享倡议（GISAID）以 FASTA 格式下载了来自 15 个不同地理区域的人类宿主中 8595 个完整的高覆盖率 SARS-CoV-2 基因组序列信息。然后，我们使用 Clustal Omega 软件对它们进行比对，并研究 UTR 变体。我们还分别使用“RBPmap”和“RNA22 v2”查看了这些区域中假定的宿主 RNA 结合蛋白（RBP）和 microRNA 结合位点。检查了选定的 RBP 和 microRNA 在肺组织中的表达状态。
我们根据最小变异百分比截止值 0.5，在 SARS-CoV-2 UTR 区域中确定了 28 个独特的变体。除了 241C>T 变化外，重要的 5'-UTR 变化是 187A>G，而 29734G>C、29742G>A/T 和 29774C>T 是大多数大陆中 3'UTR 最常见的变体。此外，我们发现，尽管 UTR 区域存在变异，但宿主 RBP 与它们的结合仍然基本不变，这进一步影响了特定 miRNAs 的功能。
我们的结果首次在 SARS-CoV-2 感染中表明，宿主 RBPs-miRNAs 和病毒 UTR 变体之间可能存在交叉对话，这最终可以解释病毒逃避宿主 RNA 降解机制的机制。这些知识可能有助于未来开发抗病毒化合物。
