Deletion of a subgroup of ribosome-related genes minimizes hypoxia-induced changes and confers hypoxia tolerance

Abstract

Deletion of a subgroup of ribosome-related genes minimizes hypoxia-induced changes and confers hypoxia tolerance. Physiol Genomics 43: 855-872, 2011. First published May 17, 2011 doi:10.1152/physiolgenomics.00232.2010.-Hypoxia is a widely occurring condition experienced by diverse organisms under numerous physiological and disease conditions. To probe the molecular mechanisms underlying hypoxia responses and tolerance, we performed a genome-wide screen to identify mutants with enhanced hypoxia tolerance in the model eukaryote, the yeast Saccharomyces cerevisiae.Yeast provides an excellent model for genomic and proteomic studies of hypoxia. 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 by using the iTRAQ profiling technology showed that a substantially fewer number of proteins were changed in response to hypoxia in the deletion mutants, compared with the parent strain. 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 the deletion strains. These results show that the 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. These results may have broad implications in understanding hypoxia responses and tolerance in diverse eukaryotes ranging from yeast to humans.genome-wide screen; proteomic analysis; iTRAQ; regulatory network; stress response LIVING ORGANISMS RANGING FROM aquatic organisms to plants and humans can experience episodes of low oxygen availability, namely, hypoxia. Hypoxia can occur in plant roots when a field is flooded, in yeast during fermentation, or in humans at high altitudes or as a result of a heart attack or stroke. Because oxygen is critical for the survival and development of many living organisms, particularly eukaryotes, living organisms ranging from yeast to humans have developed sophisticated mechanisms to respond and adapt to the changes in oxygen levels in the environment (12, 127). In the wilderness, several species, including fossorial mammals, diving animals, and birds living at high altitudes, have acquired hypoxia tolerance, which enables them to survive under conditions of limited oxygen supply (9, 84, 92). In humans, hypoxia is associated with an array of pathological conditions, such as cancer and stroke. Mechanisms of oxygen sensing and regulation have been implicated in a wide array of physiological and pathological processes (35,99,127). Thus, studying hypoxia ...

Comprehensive proteomic analysis of the main liver and attached liver of <i>Glyptosternum maculatum</i> on the basis of data-independent mass spectrometry acquisition

“…In this study, ribosome-related proteins were significantly enriched, which was consistent with the results of earlier research (Shah et al, 2011). Since organisms can conserve energy by suppressing protein synthesis, modifying ribosomal functions is an effective way to minimize hypoxia-induced protein changes and confer hypoxia tolerance (Gerasimovskaya et al, 2005).…”

Hypoxia-induced gene expression results from selective mRNA partitioning to the endoplasmic reticulum

“…mRNA translation is among the most energy-consuming processes in the cell and the majority of translational regulation occurs at the level of initiation, which is thought to be the rate-limiting step ( 13 , 14 ). It has been shown that protein synthesis has a significant impact on hypoxia tolerance, supporting the pivotal role of mRNA translation in cellular adaptation to hypoxia ( 15 , 16 ). Global suppression of protein synthesis occurs through phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2-α) and inhibition of mammalian target of rapamycin (mTOR) under prolonged hypoxia, both leading to repression of 5′-cap-dependent initiation of mRNA translation ( 17 – 19 ).…”

Human Nucleolar Protein 7 (NOL7) is required for pre-rRNA transcription and pre-18S rRNA processing

“…Bud21 is also known to be a Ty1 retrotransposon host factor 29 . Deletion of Bud21 renders increased hypoxia tolerance 30 and improved xylose carbon source utilization 31 , while Bud21 expression is upregulated upon acetic acid challenge 32 .…”

“…Bud21 is also known to be a Ty1 retrotransposon host factor 29 . Deletion of Bud21 renders increased hypoxia tolerance 30 and improved xylose carbon source utilization 31 , while Bud21 expression is upregulated upon acetic acid challenge 32 . Overall, not much is known about the molecular functions of Utp9 and Bud21 in ribosome biogenesis, even in the well-studied model organism S. cerevisiae .…”