Determining Whether the Nature of the Amino Acid Substitution or the Extent of Mistranslation Affects the Impact of Mistranslating tRNAs in Saccharomyces cerevisiae.
Abstract
Mistranslation occurs when an mRNA sequence is improperly decoded. Mistranslation can destabilize the proteome thus having a detrimental impact on the cell. tRNA variants with altered charging or decoding capabilities can increase mistranslation. Four mistranslating tRNAs were evaluated in yeast cells for their effect on growth, heat shock response, genetic interactions and cell morphology. Three of the tRNAs mistranslate at similar frequency, allowing for direct comparison of different amino acid substitutions. Each variant had distinct phenotypic consequences. Two of the tRNAs cause the same type of amino acid substitution but to different extents. The tRNA with the higher mistranslation frequency had a greater impact on the cell. These results demonstrate that the nature of the amino acid substitution and the extent of mistranslation influence the phenotype arising from a mistranslating tRNA. As the human genome contains distinct patterns of potential mistranslating tRNAs, these findings have consequences with respect to disease.