RNA dimerization plays a role in ribosomal frameshifting of the SARS coronavirus

Ishimaru, Daniella; Plant, Ewan P.; Sims, Amy C.; Yount, Boyd L.; Roth, Braden M.; Eldho, Nadukkudy V.; Pérez-Alvarado, Gabriela C.; Armbruster, David W.; Baric, Ralph S.; Dinman, Jonathan D.; Taylor, Deborah R.; Hennig, Mirko

On the basis of phylogeny clustering, CoVs are classified into three Groups (Group 1-3) . The SARS-CoV lineage has been proposed to cluster with Group 2 (44, 45) . To further analyse conservation patterns within the S3 element in a broader context, we aligned 28 complete genomic CoV sequences (summarized in Supplementary Table S1 ). As previously shown, pseudoknots containing a structured Stem 3 can be predicted for all Group 2 coronaviruses (1). The calculated average free energy for predicted Stem 3s of Group 2 CoV is ÁG = À6.8 ± 1.2 kcal/mol. Except for Feline CoV (ÁG = À5.6 kcal/ mol), all Group 1 sequences are not predicted to form stable Stem 3 substructures and are characterized by average free energies around zero (ÁG = À1.4 ± 1.7 kcal/mol). Similarly, in Group 3 coronaviruses the S3L2 region is most likely a single-stranded loop as indicated by a predicted ÁG of À1.8 kcal/mol (1). Remarkably, among the predicted S3L2 structures of all 17 Group 2 coronaviruses investigated, SARS-CoV codes for the second most labile Stem 3 with a ÁG of À4.8 kcal/ mol; only the Human CoV HKU1 Stem 3 is predicted to be less stable as indicated by its ÁG of À4.7 kcal/mol (Supplementary Figure S7) . Thus, SARS-CoV may form homodimers using its unique hexanucleotide palindromic sequence to compensate for a lack of thermodynamic stability.