tRNA thiolation links translation to stress responses in Saccharomyces cerevisiae.
tRNA thiolation links translation to stress responses in Saccharomyces cerevisiae.
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DOI：
10.1091/mbc.e14-06-1145
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发表时间：
2015-01-15
影响因子：
3.3
通讯作者：
Ploegh HL
中科院分区：
文献类型：
--
作者：
Damon JR;Pincus D;Ploegh HL
URM1途径在tRNA巯基化反应中起作用，该反应是合成tRNA中发现的mcm 5s2U34核苷所需的。酿酒酵母细胞在升高的温度下生长导致修饰酶水平改变，这导致tRNA巯基化水平降低。tRNA巯基化与细胞应激反应有关。虽然tRNA修饰已经被很好地分类，但许多修饰的确切功能及其在介导基因表达中的作用仍有待阐明。尽管tRNA修饰长期以来被认为是组成性的，但现在很明显，tRNA的修饰状态会随不同的环境条件而变化。URM1途径是酿酒酵母细胞质tRNA tGluUUC、tGlnUUG和tLysUUU巯基化所必需的。我们证明，URM1通路突变体的翻译受损，这导致增加的基础激活的Hsf1介导的热休克反应，我们还发现，在野生型细胞中的tRNA巯基化水平下降时，细胞在高温下生长。我们发现，tRNA巯基化的缺陷可以有条件地有利，赋予抵抗内质网应激。URM1途径蛋白是不稳定的，因此对细胞翻译能力的变化更敏感，这在经历应激的细胞中降低。我们提出了一个模型，其中应激诱导的翻译减少导致URM1途径组分水平降低，这导致tRNA巯基化水平降低，从而进一步减少翻译。这种机制确保了tRNA巯基化和翻译紧密耦合，并根据需要进行协同调节。
The URM1 pathway functions in a tRNA thiolation reaction that is required for synthesis of the mcm5s2U34 nucleoside found in tRNAs. Growth of Saccharomyces cerevisiae cells at an elevated temperature results in altered levels of modification enzymes, and this leads to decreased levels of tRNA thiolation. tRNA thiolation is tied to cellular stress responses. Although tRNA modifications have been well catalogued, the precise functions of many modifications and their roles in mediating gene expression are still being elucidated. Whereas tRNA modifications were long assumed to be constitutive, it is now apparent that the modification status of tRNAs changes in response to different environmental conditions. The URM1 pathway is required for thiolation of the cytoplasmic tRNAs tGluUUC, tGlnUUG, and tLysUUU in Saccharomyces cerevisiae. We demonstrate that URM1 pathway mutants have impaired translation, which results in increased basal activation of the Hsf1-mediated heat shock response; we also find that tRNA thiolation levels in wild-type cells decrease when cells are grown at elevated temperature. We show that defects in tRNA thiolation can be conditionally advantageous, conferring resistance to endoplasmic reticulum stress. URM1 pathway proteins are unstable and hence are more sensitive to changes in the translational capacity of cells, which is decreased in cells experiencing stresses. We propose a model in which a stress-induced decrease in translation results in decreased levels of URM1 pathway components, which results in decreased tRNA thiolation levels, which further serves to decrease translation. This mechanism ensures that tRNA thiolation and translation are tightly coupled and coregulated according to need.