In-Depth Bioinformatic Analyses of Nidovirales Including Human SARS-CoV-2, SARS-CoV, MERS-CoV Viruses Suggest Important Roles of Non-canonical Nucleic Acid Structures in Their Lifecycles
In-Depth Bioinformatic Analyses of Nidovirales Including Human SARS-CoV-2, SARS-CoV, MERS-CoV Viruses Suggest Important Roles of Non-canonical Nucleic Acid Structures in Their Lifecycles
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DOI：
10.3389/fmicb.2020.01583
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发表时间：
2020-07-03
影响因子：
5.2
通讯作者：
Pecinka, Petr
中科院分区：
文献类型：
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作者：
Bartas, Martin;Brazda, Vaclav;Pecinka, Petr
非典型核酸结构在分子过程的调控中发挥着重要作用。考虑到正在进行的冠状病毒危机的重要性，我们决定评估迄今为止测序的所有冠状病毒的基因组（更广泛地说，是idovirales），以确定它们是否含有非典型核酸结构。我们发现了假定的g -四重体位点和更多的反向重复（IRs）位点的证据，它们实际上在整个基因组序列中普遍存在，并表明基因组RNA包装的可能机制。对于大小为12+核苷酸的IRs，在5 ' UTR内发现了最显著的富集，而假定的四重位点（PQSs）最显著的富集位于3 ' UTR前、5 ' UTR内和mRNA之前。这表明IRs和PQSs都具有重要的调节作用。此外，我们在人蛋白中发现了多个g -四重体结合基序，具有结合SARS-CoV-2 RNA的潜力。因此，核糖核酸和新型SARS-CoV-2中的非典型核酸结构是未来可以靶向和利用的有希望的药物结构。
Non-canonical nucleic acid structures play important roles in the regulation of molecular processes. Considering the importance of the ongoing coronavirus crisis, we decided to evaluate genomes of all coronaviruses sequenced to date (stated more broadly, the orderNidovirales) to determine if they contain non-canonical nucleic acid structures. We discovered much evidence of putative G-quadruplex sites and even much more of inverted repeats (IRs) loci, which in fact are ubiquitous along the whole genomic sequence and indicate a possible mechanism for genomic RNA packaging. The most notable enrichment of IRs was found inside 5 ' UTR for IRs of size 12+ nucleotides, and the most notable enrichment of putative quadruplex sites (PQSs) was located before 3 ' UTR, inside 5 ' UTR, and before mRNA. This indicates crucial regulatory roles for both IRs and PQSs. Moreover, we found multiple G-quadruplex binding motifs in human proteins having potential for binding of SARS-CoV-2 RNA. Non-canonical nucleic acids structures inNidoviralesand in novel SARS-CoV-2 are therefore promising druggable structures that can be targeted and utilized in the future.