Search

Despite the similarity in fundamental goals of translation initiation between different domains of life, it is one of the most phylogenetically diverse steps of the central dogma of molecular biology. In a classical view, the translation signals for prokaryotes and eukaryotes are distinct from each other. This idea was challenged by the finding that the Internal Ribosome Entry Site (IRES) belonging to Plautia stali intestine virus (PSIV) could bypass the domain-specific boundaries and effectively initiate translation in E. coli. This finding led us to investigate whether the ability of PSIV IRES to initiate translation in E. coli is specific to this IRES and also to study features that allow this viral IRES to mediate prokaryotic translation initiation. We observed that certain IRESs may also possess the ability to initiate E. coli translation. Our results also indicated that the structural integrity of the PSIV IRES in translation in prokaryotes does not appear to be as critical as it is in eukaryotes. We also demonstrated that two regions of the PSIV IRES with complementarity to 16S ribosomal RNA are important for the ability of this IRES to initiate translation in E. coli.

Lithium Chloride (LiCl) toxicity, mode of action and cellular responses have been the subject of active investigations over the past decades. In yeast, LiCl treatment is reported to reduce the activity and alters the expression of PGM2, a gene that encodes a phosphoglucomutase involved in sugar metabolism. Reduced activity of phosphoglucomutase in the presence of galactose causes an accumulation of intermediate metabolites of galactose metabolism leading to a number of phenotypes including growth defect. In the current study, we identify two understudied yeast genes, YTA6 and YPR096C that when deleted, cell sensitivity to LiCl is increased when galactose is used as a carbon source. The 5'-UTR of PGM2 mRNA is structured. Using this region, we show that YTA6 and YPR096C influence the translation of PGM2 mRNA.

Heavy 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.