TY - JOUR
T1 - Survival from hypoxia in C. elegans by inactivation of aminoacyl-tRNA synthetases
AU - Anderson, Lori L.
AU - Mao, Xianrong
AU - Scott, Barbara A.
AU - Crowder, C. Michael
PY - 2009/1/30
Y1 - 2009/1/30
N2 - Hypoxia is important in a wide range of biological processes, such as animal hibernation and cell survival, and is particularly relevant in many diseases. The sensitivity of cells and organisms to hypoxic injury varies widely, but the molecular basis for this variation is incompletely understood. Using forward genetic screens in Caenorhabditis elegans, we isolated a hypoxia-resistant reduction-of-function mutant of rrt-1 that encodes an arginyl-transfer RNA (tRNA) synthetase, an enzyme essential for protein translation. Knockdown of rrt-1, and of most other genes encoding aminoacyl-tRNA synthetases, rescued animals from hypoxia-induced death, and the level of hypoxia resistance was inversely correlated with translation rate. The unfolded protein response was induced by hypoxia and was required for the hypoxia resistance of the reduction-of-function mutant of rrt-1. Thus, translational suppression produces hypoxia resistance, in part by reducing unfolded protein toxicity.
AB - Hypoxia is important in a wide range of biological processes, such as animal hibernation and cell survival, and is particularly relevant in many diseases. The sensitivity of cells and organisms to hypoxic injury varies widely, but the molecular basis for this variation is incompletely understood. Using forward genetic screens in Caenorhabditis elegans, we isolated a hypoxia-resistant reduction-of-function mutant of rrt-1 that encodes an arginyl-transfer RNA (tRNA) synthetase, an enzyme essential for protein translation. Knockdown of rrt-1, and of most other genes encoding aminoacyl-tRNA synthetases, rescued animals from hypoxia-induced death, and the level of hypoxia resistance was inversely correlated with translation rate. The unfolded protein response was induced by hypoxia and was required for the hypoxia resistance of the reduction-of-function mutant of rrt-1. Thus, translational suppression produces hypoxia resistance, in part by reducing unfolded protein toxicity.
UR - http://www.scopus.com/inward/record.url?scp=59149097747&partnerID=8YFLogxK
U2 - 10.1126/science.1166175
DO - 10.1126/science.1166175
M3 - Article
C2 - 19179530
AN - SCOPUS:59149097747
SN - 0036-8075
VL - 323
SP - 630
EP - 633
JO - Science
JF - Science
IS - 5914
ER -