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:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Crowder CM
Crowder CM
中科院分区:
其他
文献类型:
--
作者:
Anderson LL;Mao X;Scott BA;Crowder CM

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生物体及其细胞对缺氧损伤的敏感性差异很大,然而,很少有后生动物缺氧敏感性的遗传决定因素已被确定。我们在这里报告的深刻耐缺氧突变体的分离和鉴定为rrt-1,它编码一个乙酰-tRNA合成酶的功能减少的等位基因。在缺氧性损伤之前或之后的RRT-1敲低可使动物免于死亡。大多数其他氨酰-tRNA合成酶的RNAi敲低也赋予耐缺氧性,其水平与翻译速率负相关。rrt-1(RNAi)阻断低氧诱导的未折叠蛋白反应和衣霉素毒性。未折叠蛋白反应的中断部分抑制rrt-1(lf)的耐缺氧性。这些数据支持一个模型,其中翻译抑制诱导耐缺氧,部分通过减少未折叠蛋白质的毒性。
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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