Survival from Hypoxia in C. elegans by Inactivation of Aminoacyl-tRNA Synthetases

• DOI: 10.1126/science.1166175
• Publication Date: 2009-01-29T22:19:29Z
• Authors: Lori L. Anderson; Xianrong Mao; Barbara A. Scott; C. Michael Crowder
• Keywords: Hypoxia; Amino Acyl-tRNA Synthetases

Hypoxia is important in a wide range of biological processes, such as animal hibernation and cell survival, particularly relevant many diseases. The sensitivity cells organisms to hypoxic injury varies widely, but the molecular basis for this variation incompletely understood. Using forward genetic screens Caenorhabditis elegans, we isolated hypoxia-resistant reduction-of-function mutant rrt-1 that encodes an arginyl-transfer RNA (tRNA) synthetase, enzyme essential protein translation. Knockdown rrt-1, most other genes encoding aminoacyl-tRNA synthetases, rescued animals from hypoxia-induced death, level hypoxia resistance was inversely correlated with translation rate. unfolded response induced by required rrt-1. Thus, translational suppression produces resistance, part reducing toxicity.