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

A novel coronavirus was responsible for the sudden epidemic, severe acute respiratory syndrome (SARS) outbreak, in 2003. Coronaviruses are positive-strand RNA viruses with large genomes [$30 000 nucleotides (nt)] that serve as templates for translation of viral proteins and for replication. The production of proteins from these viral RNAs does not follow the usual rules governing translation. The first polyprotein encoded by open reading frame (ORF)1a, which encodes non-structural proteins, is defined by initiation and termination codons and is translated normally. Signals embedded within the RNA just before the termination codon of ORF1a redirect a fraction of translating ribosomes to bypass the stop codon and continue translation in the -1 reading frame, thus creating the larger ORF1ab polyprotein (1-3). These programmed -1 ribosomal frameshift (-1 PRF) stimulating signals are typically composed of a heptameric slippery site, on which the ribosome can change register by 1 nt in the 5 0 direction, followed by a pseudoknot. Slippery site sequence requirements have been characterized for several cell types (4) but the range and diversity of frameshift-stimulating pseudoknots continues to grow (5) .