Survival from hypoxia in C. elegans by inactivation of aminoacyl-tRNA synthetases.
Survival from hypoxia in C. elegans by inactivation of aminoacyl-tRNA synthetases.
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DOI:
10.1126/science.1166175
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发表时间:
2009-01-30
期刊:
影响因子:
--
通讯作者:
Crowder CM
中科院分区:
文献类型:
--
作者:
Anderson LL;Mao X;Scott BA;Crowder CM
The sensitivity of an organism and its cells to hypoxic injury varies widely; yet, few genetic determinants of metazoan hypoxic sensitivity have been identified. We report here the isolation of a profoundly hypoxia resistant mutant and its identification as a reduction-of-function allele of rrt-1, which encodes an arginyl-tRNA synthetase. rrt-1 knockdown before or after the hypoxic injury rescues animals from death. RNAi knockdown of most other aminoacyl-tRNA synthetases also confers hypoxia resistance, the level of which inversely correlates with translation rate. rrt-1(RNAi) blocked hypoxic induction of the unfolded protein response and tunicamycin toxicity. Disruption of the unfolded protein response partially suppressed the hypoxia resistance of rrt-1(lf). The data support a model where translational suppression induces hypoxia resistance, in part by reducing unfolded protein toxicity.
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