THE MOF2 SUI1 PROTEIN IS A GENERAL MONITOR OF TRANSLATIONAL ACCURACY/

Although it is essential for protein synthesis to be highly accurate, a number of cases of directed ribosomal frameshifting have been report ed in RNA viruses, as well as in procaryotic and eucaryotic gents, Cha nges in the efficiency of ribosomal frameshifting can have major effec ts on the ability of cells to propagate viruses,which use this mechani sm, Furthermore, studies of this process can illuminate the mechanisms involved in the maintenance of the normal translation reading frame, The yeast Saccharomyces cerevisiae killer virus system uses programmed -1 ribosomal frameshifting to synthesize its gene products, Strains h arboring the mof2-1 allele demonstrated a fivefold increase in framesh ifting and prevented killer virus propagation, In this report, we pres ent the results of the cloning and characterization of the wild-type M OF2 gene, mof2-1 is a novel allele of SUI1, a gene previously shown to play a role in translation initiation start site selection, Strains h arboring the mof2-1 allele demonstrated a mutant start site selection phenotype and increased efficiency of programmed -1 ribosomal frameshi fting and conferred paromomycin sensitivity, The increased frameshifti ng observed in vivo was reproduced in extracts prepared from mof2-1 ce lls, Addition of purified wild-type Mof2p/Sui1p reduced frameshifting efficiencies to wild-type levels, Expression of the human SUI1 homolog in yeast corrects all of the mof2-1 phenotypes, demonstrating that th e function of this protein is conserved throughout evolution, Taken to gether, these results suggest that Mof2p/Sui1p functions as a general modulator of accuracy at both the initiation and elongation phases of translation.