Ribosomal frameshifting on viral RNAs

Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK Introduction. Accurate maintenance of the translational reading frame by ribosomes is essential for the production of functional proteins and unsurprisingly, errors in frame maintenance have been estimated to occur at rates probably lower than 5 x 10 -5 per codon (Kurland, 1992). However, an increasing number of examples have been documented where a purposeful shift in reading frame is programmed into the mRNA and serves an essential function (Gesteland et al. , 1992; Atkins & Gesteland, 1995). Highly efficient ribosomal frameshifting is an example of such a programmed frameshift site. In response to certain signals in the mRNA, ribosomes are induced to move into the -1 reading frame (in a 5' direction) at a specific point and continue translation in the new reading frame. The phenomenon was first described in 1985 as the way in which the Gag-Pol polyprotein of the retrovirus Rous sarcoma virus (RSV) is expressed from the overlapping gag and pol open reading frames (ORFs) (Jacks & Varmus, 1985) and to date, most examples of frameshifting come from virus systems. * Fax +44 1223 336926. e-mail ib103@mole.bio.cam.ac.uk