Coordinate Regulation of Ribosome and tRNA Biogenesis Controls Hypoxic Injury and Translation.
Coordinate Regulation of Ribosome and tRNA Biogenesis Controls Hypoxic Injury and Translation.
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核糖体和TRNA生物发生的坐标调节可控制低氧损伤和翻译。
DOI：
10.1016/j.cub.2020.10.001
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发表时间：
2021-01-11
期刊：
影响因子：
--
通讯作者：
Crowder CM
中科院分区：
文献类型：
--
作者：
Itani OA;Zhong X;Tang X;Scott BA;Yan JY;Flibotte S;Lim Y;Hsieh AC;Bruce JE;Van Gilst M;Crowder CM
翻译机器由无数的蛋白质和RNA组成，其水平必须协调以有效地产生蛋白质而不浪费能量或底物。然而，蛋白质合成显然并不总是完美地适应其环境，因为翻译机器组件的中断可以延长寿命并对生存造成压力。虽然从细菌和酵母菌中了解到了很多关于翻译调控的知识，但在后生动物中了解的却少得多。在筛选保护C.从缺氧胁迫中分离出多个影响蛋白质合成的基因：核糖体RNA解旋酶基因、tRNA生物合成基因和控制氨基酸可用性的基因。为了更好地定义这些基因影响蛋白质合成的机制，我们进行了第二次筛选RNA解旋酶突变体的条件性发育停滞表型的抑制因子，并确定了参与核糖体生物合成的基因。令人惊讶的是，这些抑制突变恢复正常的缺氧敏感性和蛋白质合成的tRNA生物合成突变体，但不突变减少氨基酸摄取。蛋白质组学分析表明，减少tRNA生物合成活性产生的核糖体亚基的选择性稳态减少，从而提供了一种抑制结果的机制。我们的研究揭示了一种未被认识的高阶翻译调控机制，在后生动物，核糖体生物发生基因与控制tRNA丰度的基因通信匹配的全球蛋白质合成速率与可用资源。在线虫C. Itani等人在elegans中寻找耐缺氧细胞损伤的突变体，Itani等人在翻译机制中分离出多个基因的突变。随后的遗传学和蛋白质组学实验使我们偶然发现了tRNA和核糖体生物合成之间的反馈机制。
The translation machinery is composed of a myriad of proteins and RNAs whose levels must be coordinated to produce efficiently proteins without wasting energy or substrate. However, protein synthesis is clearly not always perfectly tuned to its environment as disruption of translation machinery components can lengthen lifespan and stress survival. While much has been learned from bacteria and yeast about translational regulation, much less is known in metazoans. In a screen for mutations protecting C. elegans from hypoxic stress, we isolated multiple genes impacting protein synthesis: a ribosomal RNA helicase gene, tRNA biosynthesis genes, and a gene controlling amino acid availability. To define better the mechanisms by which these genes impact protein synthesis, we performed a second screen for suppressors of the conditional developmental arrest phenotype of the RNA helicase mutant and identified genes involved in ribosome biogenesis. Surprisingly, these suppressor mutations restored normal hypoxic sensitivity and protein synthesis to the tRNA biogenesis mutants, but not to the mutant reducing amino acid uptake. Proteomic analysis demonstrated that reduced tRNA biosynthetic activity produces a selective homeostatic reduction in ribosomal subunits, thereby offering a mechanism for the suppression results. Our study uncovers an unrecognized higher order translation regulatory mechanism in a metazoan whereby ribosome biogenesis genes communicate with genes controlling tRNA abundance matching the global rate of protein synthesis with available resources. In a screen in the nematode C. elegans for mutants that are resistant to hypoxic cellular injury, Itani et al. isolate mutations in multiple genes in the translation machinery. Subsequent genetic and proteomic experiments lead to our serendipitous discovery of a feedback mechanism between tRNA and ribosome biogenesis.
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
Science (New York, N.Y.)
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