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 systems^6,7. 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.