Deletion of a Subgroup of Ribosome‐related Genes Minimizes Hypoxia‐induced Changes and Confers Hypoxia Tolerance in Saccharomyces Cerevisiae

Hypoxia is a widely occurring condition experienced by diverse organisms under numerous physiological and disease conditions. Here, to probe the molecular mechanisms underlying hypoxia responses and tolerance, we performed a genome‐wide screen to identify mutants with enhanced hypoxia tolerance in yeast. We identified five genes whose deletion significantly enhanced hypoxia tolerance. They are RAI1, NSR1, BUD21, RPL20A, and RSM22, all of which encode functions involved in ribosome biogenesis. Further analysis of the deletion mutants showed that they minimized hypoxia‐induced changes in polyribosome profiles and protein synthesis. Strikingly, proteomic analysis using the iTRAQ profiling technology showed that hypoxia induced changes in a substantially fewer number of proteins in the deletion mutants. Computational analysis of the iTRAQ data indicated that the activities of a group of regulators were regulated by hypoxia in the wild type parent cells, but such regulation appeared to be diminished in deletion strains. These results show that deletion of one of the genes involved in ribosome biogenesis leads to the reversal of hypoxia‐induced changes in gene expression and related regulators. They suggest that modifying ribosomal function is an effective mechanism to minimize hypoxia‐induced specific protein changes and to confer hypoxia tolerance.