Identification and enrichment of SECReTE cis-acting RNA elements in the Coronaviridae and other (+) single-strand RNA viruses

Gal Haimovich; Tsviya Olender; Camila Baez; Jeffrey E Gerst

Interestingly, NL63 may be more pathogenic than the other endemic hCoVs, although this supposition is based upon a very limited number of reports totaling less than 200 cases world-wide [19] [20] [21] [22] [23] [24] [25] , and hence its inclusion in the highly pathogenic hCoV group is pending more research (Supplementary Figure S1) . Overall, we could not form a definitive association between SECReTE score and hCoV pathogenicity. Interestingly, however, we could begin identify several potential phenomenon related to SECReTE presence in both viral and human genes. First, we observed that SECReTE positions within the hCoV Spike protein showed co-occurrence (Supplementary Figure S2 and Supplementary Table S1 ). This suggests that motif presence could be positionally conserved, although the mechanism by which this happens (i.e. conservation vs. drift vs. convergence) is not known. Nevertheless, it suggests a functional requirement for SECReTE in some aspect of either S gene RNA association with membranes or in Spike protein translation, or perhaps both. Further work is necessary to reveal the role (if any) of SECReTE motifs in hCoV RNA association with ER membranes or the translation of viral proteins, not only for the S gene, The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.20.050088 doi: bioRxiv preprint but for all other structural and non-structural protein-encoding genes containing this motif. Since SECReTE presence or absence significantly affected the synthesis and secretion of three yeast proteins examined (Suc2, Hsp150, and Ccw12), as well as an exogenously expressed form of secretion-competent GFP in yeast 6 , we presume that the motif may fulfill a similar role in the production of viral proteins. Second, we determined that certain families of human proteins are enriched with SECReTE motifs more than random occurrence (Figure 4) .