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Mol Cell Biol, March 1998, p. 1506-1516, Vol. 18, No. 3
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Mof2/Sui1 Protein Is a General Monitor of Translational Accuracy

Ying Cui,1 Jonathan D. Dinman,1,2 Terri Goss Kinzy,1,2 and Stuart W. Peltz1,2,3,*

Department of Molecular Genetics and Microbiology1 and Graduate Program in Molecular Biosciences at UMDNJ/Rutgers Universities,2 Robert Wood Johnson Medical School-UMDNJ, and Cancer Institute of New Jersey,3 Piscataway, New Jersey 08854

Received 17 September 1997/Returned for modification 3 November 1997/Accepted 23 November 1997

Although it is essential for protein synthesis to be highly accurate, a number of cases of directed ribosomal frameshifting have been reported in RNA viruses, as well as in procaryotic and eucaryotic genes. Changes in the efficiency of ribosomal frameshifting can have major effects on the ability of cells to propagate viruses which use this mechanism. 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 harboring the mof2-1 allele demonstrated a fivefold increase in frameshifting and prevented killer virus propagation. In this report, we present the results of the cloning and characterization of the wild-type MOF2 gene. mof2-1 is a novel allele of SUI1, a gene previously shown to play a role in translation initiation start site selection. Strains harboring the mof2-1 allele demonstrated a mutant start site selection phenotype and increased efficiency of programmed -1 ribosomal frameshifting and conferred paromomycin sensitivity. The increased frameshifting observed in vivo was reproduced in extracts prepared from mof2-1 cells. 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 the function of this protein is conserved throughout evolution. Taken together, these results suggest that Mof2p/Sui1p functions as a general modulator of accuracy at both the initiation and elongation phases of translation.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School-UMDNJ, 675 Hoes Lane, Piscataway, NJ 08854. Phone: (732) 235-4790. Fax: (732) 235-5223. E-mail: Peltz{at}RWJA.UMDNJ.EDU.




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