In-depth Bioinformatic Analyses of Human SARS-CoV-2, SARS-CoV, MERS-CoV, and Other Nidovirales Suggest Important Roles of Noncanonical Nucleic Acid Structures in Their Lifecycles

Martin Bartas; Václav Brázda; Natália Bohálová; Alessio Cantara; Adriana Volná; Tereza Stachurová; Katerina Malachová; Eva B. Jagelská; Otília Porubiaková; Jirí Cerven; Petr Pecinka

Using the RBPmap tool, we predicted human RNA-binding proteins sites in SARS-CoV-2 RNA. While holding to very stringent thresholds, three highly promising candidate human RNA-binding proteins were predicted. SRSF7 was predicted to bind viral RNA in nucleotide position 26, 199 (NC_045512.2), which is in fact exactly the binding motif for this protein (ACGACG). Protein HNRNPA1 was predicted to bind viral RNA in nucleotide position 23,090-23 097 (exact binding motif GUAGUAGU). The last protein found was TRA2A in nucleotide position 3,056-3,065 and position 3,074-3,083, in both cases with one mismatch (the motifs found were GAAGAAGAAG and the experimentally validated motif for TRA2A is GAAGAGGAAG). All three of these proteins share multiple RGG-rich novel interesting quadruplex interaction (NIQI) motifs, which are common to most human G-quadruplex-binding proteins (Brázda et al., 2018; Huang et al., 2018; Masuzawa and Oyoshi, 2020) . All find individual motif occurrence (FIMO) hits below p-value = 1.10 -4 are enclosed in Supplementary Material 7. The proteins SRSF7, HNRNPA1, and TRA2A are involved in mRNA splicing via the spliceosome pathway (Szklarczyk et al., 2015) .