Heavy metal sensitivities of gene deletion strains forITT1andRPS1Aconnect their activities to the expression ofURE2, a key gene involved in metal detoxification in yeast

AbstractHeavy metal and metalloid contaminations are among the most concerning types of pollutant in the environment. Consequently, it is important to investigate the molecular mechanisms of cellular responses and detoxification pathways for these compounds in living organisms. To date, a number of genes have been linked to the detoxification process. The expression of these genes can be controlled at both transcriptional and translational levels. In baker’s yeast,Saccharomyces cerevisiae, resistance to a wide range of toxic metals is regulated by glutathione S-transferases. YeastURE2encodes for a protein that has glutathione peroxidase activity and is homologous to mammalian glutathione S-transferases. TheURE2expression is critical to cell survival under heavy metal stress. Here, we report on the finding of two genes,ITT1, an inhibitor of translation termination, andRPS1A, a small ribosomal protein, that when deleted yeast cells exhibit similar metal sensitivity phenotypes to gene deletion strain forURE2. Neither of these genes were previously linked to metal toxicity. Our gene expression analysis illustrates that these two genes affectURE2mRNA expression at the level of translation.Summary statementWe identified two yeast genes,ITT1andRPS1A, that when deleted, results in yeast cells sensitivity to heavy metals and metalloids. Further investigation indicated that they influence the expression ofURE2gene, a key player in metal detoxification, by upregulating its translation. Our findings suggest thatITT1andRPS1Aplay an indirect role in responding to toxic metal stress.