Schwenzer, H;
Jühling, F;
Chu, A;
Pallett, LJ;
Baumert, TF;
Maini, M;
Fassati, A;
(2019)
Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response.
Cell Reports
, 26
(12)
3416-3428.e5.
10.1016/j.celrep.2019.02.077.
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Abstract
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 tRNASeC, 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.
| Type: | Article |
|---|---|
| Title: | Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2019.02.077 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2019.02.077 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | PKR, REDD1, fluorescence in situ hybridization, mTOR, nucleus, oxidative stress, retrograde transport, tRNA, unfolded protein response |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10071012 |
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