Phenotypic suppression and misreading in Saccharomyces cerevisiae

Abstract

A NUMBER of antibiotics and other inhibitors have been useful in genetic and biochemical analyses of the protein-synthesising machinery of prokaryotic and eukaryotic organisms. Aminoglycoside antibiotics have been shown to be particularly helpful in this respect, especially in identifying ribosomal protein cistrons in bacteria. The aminoglycosides cause extensive misreading of the RNA code words in vitro1 and suppress many nonsense and missense mutations in E. coli2 phenotypically. The misreading observed in cell-free translation is believed to be the basis for the phenotypic suppression, although the exact mechanism is not known. Apart from a report of suppression of a single mutation in yeast by streptomycin3, there have been no demonstrations of phenotypic suppression in eukaryotic organisms. Earlier studies of mistranslation in vitro in eukaryotic systems indicated that this phenomenon is rare. Streptomycin did not cause misreading with cytoplasmic ribosomes of rat liver4, rabbit spleen5, chicken liver6 or yeast7; neomycin had no effect in rabbit reticulocyte extracts4 and only a slight effect in the yeast and chicken liver systems6,7. These results suggested that translation in higher organisms functions with higher fidelity than that in bacteria. Nevertheless, aminoglycoside antibiotics have recently been shown to cause extensive translational misreading in vitro in systems derived from Tetrahymena8, wheat embryo9, and cultured human cells10.