Translational gymnastics on the Sendai virus P/C mRNA

The Sendai virus (SeV) P/C mRNA expresses eight different polypeptide chains using a combination of ribosomal choice and cotranscriptional editing (an internal open reading frame (ORF) is accessed by the addition of a single G residue after a short run of Gs at position 1053 on the mRNA). The longest ORF within the mRNA starts at ATG104 (the second initiation site) and encodes the 568-aa P protein, an essential viral structural protein which serves both as a cofactor for the RNA-dependant RNA polymerase (L protein) and as a part of the assembly complex. The first (ACG81), third (ATG114), fourth (ATG183) and fifth (ATG201) initiation sites are used to express a C-terminal nested set of polypeptides which are in the +1 ORF relative to P, namely C' C, Y1, and Y2, respectively (collectively named the C proteins). Leaky scanning accounts for translational initiation at the first three start sites (8 non-ATG followed by ATGs in progressively stronger contexts). Consistent with this, changing the C' ACG to an ATG (GCCATG81G; ATG81/C') ablates all expression from the downstream ATG104/P and ATG114/C initiation codons, whereas initiation from ATG183/Y1 and ATG201/Y2 remains normal in this background. Initiation from ATG183/Y1/ATG201/Y2 probably takes place by discontinuous scanning via a ribosomal shunt. Scanning complexes appear to assemble at the 5' cap and then scan the first similar to 30 nt of the 5' UTR before being translocated to an acceptor site close to the Y initiation codons. No specific 5' UTR or donor site sequence elements are required, and translation of the Y proteins continues even when their start codons are changed to ACG. (C) 1998 Academic Press.