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

Abstract

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 order Nidovirales) 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 in Nidovirales and in novel SARS-CoV-2 are therefore promising druggable structures that can be targeted and utilized in the future.

Role of SARS-CoV-2 in Altering the RNA-Binding Protein and miRNA-Directed Post-Transcriptional Regulatory Networks in Humans

“…Our results showed an enrichment for RBPs such as SRSFs, PCBPs, ELAVs, and HNRNPs being most likely to get sponged on the viral genome ( Figure 4 B). Our observation that specific RBPs such as SRSF7, HNRNPA1, and TRA2A with a well-known role in splicing exhibiting binding sites on SARS-CoV-2 RNA is in agreement with a recently published study [ 85 ]. We found that most of these RBPs were abundantly expressed in gonadal tissues; adrenal tissues; the pancreas; and immune cells, including B cells, CD4+ T cells, and NK cells ( Figure 4 B).…”

Role of SARS-CoV-2 in altering the RNA binding protein and miRNA directed post-transcriptional regulatory networks in humans

“…4B ). Specifically, our observation of RBPs well known for their role in splicing such as SRSF7, HNRNPA1 and TRA2A was in accordance with a recently published study that predicted binding sites of these RBPs on SARS-CoV-2 RNA [ 65 ]. In summary, these findings suggest that SARS-CoV-2 could sponge human RBPs on its genome resulting in altered post-transcriptional gene regulatory network in the host cells.…”

“…4B). Our observation that specific RBPs such as SRSF7, HNRNPA1 and TRA2A with well-known role in splicing exhibited binding sites on SARS-CoV-2 RNA, is in agreement with a recently published study [85]. We found that most of these RBPs were abundantly expressed in gonadal tissues, adrenal tissues, pancreas, and immune cells including B cells, CD4+ T cells and NK cells (Fig.…”

Evolutionary dynamics of the SARS-CoV-2 ORF8 accessory gene

“…The propensity of the ORF8 region to suffer deletions has raised the hypothesis that RNA secondary structures could play a role in their formation ( Consortium, 2004 ). Several hairpin structures have been already detected in SARS-CoV-2 ( Andrews et al, 2020 ; Bartas et al, 2020 ; Lan et al, 2020 ; Rangan et al, 2020 ; Simmonds, 2020 ).…”