Effect of cadmium on mRNA mistranslation in Saccharomyces cerevisiae

Although highly accurate molecular processes and various messenger RNA (mRNA) quality control and ribosome proofreading mechanisms are used by organisms to transcribe their genes and maintain the fidelity of genetic information, errors are inherent in all biological systems. Low-level translation errors caused by an imbalance of homologous and nonhomologous amino acids caused by stress conditions are particularly common. Paradoxically, advantageous phenotypic diversity can be generated by such errors in eukaryotes through unknown molecular processes. Here, we found that the significant cadmium-resistant phenotype was correlated with an increased mistranslation rate of the mRNA in Saccharomyces cerevisiae. This phenotypic change was also related to endogenous sulfur amino acid starvation. Compared with the control, the mistranslation rate caused by cadmium was significantly increased (p < .01). With the increase of cysteine contents in medium, the mistranslation rate of WT(BY4742a) decreased significantly (p < .01). This demonstrates that cadmium treatment and sulfur amino acid starvation both can induce translation errors. Although cadmium uptake is independent of the Sul1 transporter, cadmium-induced mRNA mistranslation is dependent on the sulfate uptake of the Sul1p transporter. Furthermore, cadmium-induced translation errors depend on methionine biosynthesis. Taken together, cadmium causes endogenous sulfur starvation, leading to an increase in the mRNA mistranslation, which contributes to the resistance of yeast cells to cadmium. We provide a new pathway mediating the toxicity of cadmium, and we propose that altering mRNA mistranslation may portray a different form of environmental adaptation.