Division of Infection and Immunity, University College London (UCL), London WC1E 6BT, UK.
INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 2 Université de Strasbourg, 67000 Strasbourg, France.
Cell Rep. 2019 Mar 19;26(12):3416-3428.e5. doi: 10.1016/j.celrep.2019.02.077.
In eukaryotes, tRNAs are transcribed in the nucleus and exported to the cytosol, where they deliver amino acids to ribosomes for protein translation. This nuclear-cytoplasmic movement was believed to be unidirectional. However, active shuttling of tRNAs, named tRNA retrograde transport, between the cytosol and nucleus has been discovered. This pathway is conserved in eukaryotes, suggesting a fundamental function; however, little is known about its role in human cells. Here we report that, in human cells, oxidative stress triggers tRNA retrograde transport, which is rapid, reversible, and selective for certain tRNA species, mostly with shorter 3' ends. Retrograde transport of tRNA, which promotes translation of selenoproteins required to maintain homeostatic redox levels in cells, is highly efficient. tRNA retrograde transport is regulated by the integrated stress response pathway via the PERK-REDD1-mTOR axis. Thus, we propose that tRNA retrograde transport is part of the cellular response to oxidative stress.
在真核生物中，tRNA 在细胞核中被转录，并输出到细胞质中，在那里它们将氨基酸递送到核糖体以进行蛋白质翻译。这种核质运动被认为是单向的。然而，已经发现 tRNA 在细胞质和细胞核之间的主动穿梭，称为 tRNA 逆行运输。该途径在真核生物中是保守的，表明其具有基本功能；然而，人们对其在人类细胞中的作用知之甚少。在这里，我们报告在人类细胞中，氧化应激触发 tRNA 逆行运输，该运输是快速、可逆的，并且对某些 tRNA 种类具有选择性，这些 tRNA 种类主要具有较短的 3'端。tRNA 的逆行运输促进了硒蛋白的翻译，这些硒蛋白对于维持细胞内的稳态氧化还原水平是必需的，其效率非常高。tRNA 逆行运输受到整合应激反应途径的调节，通过 PERK-REDD1-mTOR 轴进行调节。因此，我们提出 tRNA 逆行运输是细胞对氧化应激反应的一部分。
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