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.
Department of Molecular Genetics and
Microbiology1 and
Graduate Program in
Molecular Biosciences at UMDNJ/Rutgers
Universities,
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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