RNA genome conservation and secondary structure in SARS-CoV-2 and SARS-related viruses

Figures

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  Figure 1:. We aim to provide a series of genome regions in SARS-CoV-2 that are useful for a variety of diagnostic and therapeutic strategies, including regions that are (A) conserved in SARS-related betacoronaviruses and SARS-CoV-2 sequences (Table 1), (B) regions that are structured and conserved in SARS-CoV-2 sequences (Table 2), and (C) regions that are unstructured and conserved in SARS-CoV-2 sequences (Table 3).

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  Figure 2:. In black we annotate SARSr-MSA-1 conserved regions of the genome, superimposed on SARS-CoV-2 genome ORFs. We depict the top secondary structures as ranked by Matthews correlation coefficient that overlap with these conserved regions, ordered from A to E. Regions A to E are annotated on the genome in yellow and are located at genome positions: A:13743–13798, B:17511–17566, C:28990–29054, D:172–236, E:26–109. Secondary structures are colored by sequence conservation in SARSr-MSA-1 (cyan = more conserved, purple = less conserved). In magenta are depicted curated Rfam families present in coronaviruses, including the frame-shifting element (FSE), the 3´ UTR pseudoknot (PK3), and the 3´ stem-loop II-like motif (s2m). Figures prepared in Geneious41 and draw_rna (https://github.com/DasLab/draw_rna).

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  Figure 3:. Structured (cyan) and unstructured (yellow) intervals on the genome ORFs for SARS-CoV-2, predicted from RNAz and a Contrafold 2.0 analysis, respectively. (A-C) highlight the three secondary structures for windows that do not overlap with known Rfam or literature-annotated structures with the highest P-value scores from RNAz (all P>0.9). These windows are located at genome positions 14207–14366 (A), 17126–17245 (B), and 26176–26295 (C). Secondary structures are colored by sequence conservation (cyan = more conserved, purple = less conserved). Figures prepared in Geneious41 and draw_rna (https://github.com/DasLab/draw_rna).

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  Figure 4.. Secondary structure diagrams for A) 5´ UTR, B) Frameshift element, C) 3´ UTR. Nucleotides are black if 100% conserved in the SARS, bat, and SARS-CoV-2 sequences in SARSr-MSA-1, and grey otherwise. Special labeled domains are in boldface. Structures are based primarily on manual identification of homology with literature coronavirus structure models. Note that numbering in (C) is relative to 3´ end of virus sequence. Figures prepared in RiboDraw (https://github.com/ribokit/RiboDraw).

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  Figure 5.. We depict the predicted number of structured, unstructured and conserved intervals for a choice of sequence conservation cutoffs. The SARS-related conserved intervals are all regions of at least 15 nucleotides with each position at least 90% conserved across an alignment of SARS, bat coronavirus, and SARS-CoV-2 sequences (SARSr-MSA-1). The SARS-CoV-2 intervals are regions of at least 15 nucleotides with each position at least 97% conserved across an alignment of currently available SARS-CoV-2 sequences (SARS-CoV-2-MSA-2). Structured intervals are loci predicted from RNAz with some loci containing multiple RNAz windows, and unstructured intervals are stretches of at least 15 nucleotides where all bases have base-pairing probability at most 0.4. All interval intersections are required to have at least 15 nucleotide overlaps, with the number of overlapping intervals listed for each interval type involved in the intersection. Top-scoring structured intervals conserved in SARS-CoV-2 sequences (green) are listed in Table 2. Top-scoring unstructured intervals conserved in SARS-CoV-2 sequences (blue) are listed in Table 3.