Self-protective responses to norvaline-induced stress in a leucyl-tRNA synthetase editing-deficient yeast strain.
Self-protective responses to norvaline-induced stress in a leucyl-tRNA synthetase editing-deficient yeast strain.
复制标题
DOI：
10.1093/nar/gkx487
复制
发表时间：
2017-07-07
影响因子：
14.9
通讯作者：
Wang ED
中科院分区：
文献类型：
--
作者：
Ji QQ;Fang ZP;Ye Q;Chi CW;Wang ED
氨酰-tRNA合成酶（aaRSs）的编辑功能对于正确的氨酰-tRNA的形成是必不可少的。编辑缺陷可能导致生长抑制和各种疾病的发病机制。在此，我们证实，正缬氨酸（Nva），而不是异亮氨酸或缬氨酸是主要的威胁的编辑功能的酿酒酵母亮氨酰-tRNA合成酶（ScLeuRS），在体外和体内。Nva可能被错误地掺入LeuRS编辑缺陷型酵母菌株（D419 A/ScΔleuS）的蛋白质组中，可能导致功能失调的蛋白质折叠和生长延迟。此外，Nva诱导的D419 A/ScΔleuS细胞内应激反应机制的探索表明，Hsp 70分子伴侣在响应潜在的蛋白质错误折叠时显著上调。此外，脯氨酸（Pro），谷氨酸（Glu）和谷氨酰胺（Gln），这可能是由于Nva的转换积累，共同有助于减少活性氧（ROS）水平在Nva处理的D419 A/ScΔleuS细胞。总之，我们的研究突出了LeuRS编辑功能的重要性，并为理解阿尔斯编辑缺陷生物体中触发的细胞内应激保护机制提供了线索。
The editing function of aminoacyl-tRNA synthetases (aaRSs) is indispensible for formation of the correct aminoacyl-tRNAs. Editing deficiency may lead to growth inhibition and the pathogenesis of various diseases. Herein, we confirmed that norvaline (Nva) but not isoleucine or valine is the major threat to the editing function of Saccharomyces cerevisiae leucyl-tRNA synthetase (ScLeuRS), both in vitro and in vivo. Nva could be misincorporated into the proteome of the LeuRS editing-deficient yeast strain (D419A/ScΔleuS), potentially resulting in dysfunctional protein folding and growth delay. Furthermore, the exploration of the Nva-induced intracellular stress response mechanism in D419A/ScΔleuS revealed that Hsp70 chaperones were markedly upregulated in response to the potential protein misfolding. Additionally, proline (Pro), glutamate (Glu) and glutamine (Gln), which may accumulate due to the conversion of Nva, collectively contributed to the reduction of reactive oxygen species (ROS) levels in Nva-treated D419A/ScΔleuS cells. In conclusion, our study highlights the significance of the editing function of LeuRS and provides clues for understanding the intracellular stress protective mechanisms that are triggered in aaRS editing-deficient organisms.