Misactivation of multiple starvation responses in yeast by loss of tRNA modifications
Misactivation of multiple starvation responses in yeast by loss of tRNA modifications
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DOI：
10.1093/nar/gkaa455
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发表时间：
2020-07-27
影响因子：
14.9
通讯作者：
Klassen, Roland
中科院分区：
文献类型：
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作者：
Bruch, Alexander;Laguna, Teresa;Klassen, Roland
此前，不同反密码子环修饰的联合丢失被证明会损害酿酒酵母中不同 tRNA 的功能。令人惊讶的是，每种情况都会导致共享的细胞表型，其基础尚不清楚。由于 tRNA 修饰的丢失可能会引起转录反应，因此我们对具有 tRNA(UUG)(Gln) 或 tRNA(UUU)(Lys) 功能缺陷的修饰突变体的全局转录模式进行了表征。我们观察到突变体在指数生长期不恰当地诱导多种饥饿反应，包括葡萄糖和氮分解代谢物抑制基因的去抑制。此外，突变体中的自噬过早且未充分激活。我们进一步证明，当tRNA（UUG）（Gln）或tRNA（UUU）（Lys）（缺乏感兴趣的修饰的tRNA种类）过度表达时，个体饥饿基因的不当诱导以及tRNA修饰突变体形成蛋白质聚集体的倾向会减弱。因此，我们的数据表明，mRNA 翻译和蛋白质稳态的整体变化解释了转录应激特征，这些转录应激特征通常是由不同 tRNA 中反密码子修饰的丢失引发的。
Previously, combined loss of different anticodon loop modifications was shown to impair the function of distinct tRNAs in Saccharomyces cerevisiae. Surprisingly, each scenario resulted in shared cellular phenotypes, the basis of which is unclear. Since loss of tRNA modification may evoke transcriptional responses, we characterized global transcription patterns of modification mutants with defects in either tRNA(UUG)(Gln) or tRNA(UUU)(Lys) function. We observe that the mutants share inappropriate induction of multiple starvation responses in exponential growth phase, including derepression of glucose and nitrogen catabolite-repressed genes. In addition, autophagy is prematurely and inadequately activated in the mutants. We further demonstrate that improper induction of individual starvation genes as well as the propensity of the tRNA modification mutants to form protein aggregates are diminished upon overexpression of tRNA(UUG)(Gln) or tRNA(UUU)(Lys), the tRNA species that lack the modifications of interest. Hence, our data suggest that global alterations in mRNA translation and proteostasis account for the transcriptional stress signatures that are commonly triggered by loss of anticodon modifications in different tRNAs.