Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response
Summary: 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, bet...
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doaj-958f4e2d57504f1a9ede9db554104a3b2020-11-25T01:04:37ZengElsevierCell Reports2211-12472019-03-01261234163428.e5Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress ResponseHagen Schwenzer0Frank Jühling1Alexander Chu2Laura J. Pallett3Thomas F. Baumert4Mala Maini5Ariberto Fassati6Division of Infection and Immunity, University College London (UCL), London WC1E 6BT, UKINSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 2 Université de Strasbourg, 67000 Strasbourg, FranceDivision of Infection and Immunity, University College London (UCL), London WC1E 6BT, UKDivision of Infection and Immunity, University College London (UCL), London WC1E 6BT, UKINSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 2 Université de Strasbourg, 67000 Strasbourg, France; Nouvel Hôpital Civil, Institut Hospitalo-Universitaire, 67000 Strasbourg, FranceDivision of Infection and Immunity, University College London (UCL), London WC1E 6BT, UKDivision of Infection and Immunity, University College London (UCL), London WC1E 6BT, UK; Corresponding authorSummary: 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. : Schwenzer et. al discovered that oxidative stress induces nuclear import of cytoplasmic tRNAs. The authors found that this pathway is activated during the integrated stress response. tRNA nuclear import was selective to certain tRNA species and may contribute to the changes in protein translation known to protect cells from stress. Keywords: tRNA, retrograde transport, nucleus, oxidative stress, fluorescence in situ hybridization, unfolded protein response, mTOR, REDD1, PKRhttp://www.sciencedirect.com/science/article/pii/S2211124719302633 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hagen Schwenzer Frank Jühling Alexander Chu Laura J. Pallett Thomas F. Baumert Mala Maini Ariberto Fassati |
spellingShingle |
Hagen Schwenzer Frank Jühling Alexander Chu Laura J. Pallett Thomas F. Baumert Mala Maini Ariberto Fassati Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response Cell Reports |
author_facet |
Hagen Schwenzer Frank Jühling Alexander Chu Laura J. Pallett Thomas F. Baumert Mala Maini Ariberto Fassati |
author_sort |
Hagen Schwenzer |
title |
Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response |
title_short |
Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response |
title_full |
Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response |
title_fullStr |
Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response |
title_full_unstemmed |
Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response |
title_sort |
oxidative stress triggers selective trna retrograde transport in human cells during the integrated stress response |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2019-03-01 |
description |
Summary: 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. : Schwenzer et. al discovered that oxidative stress induces nuclear import of cytoplasmic tRNAs. The authors found that this pathway is activated during the integrated stress response. tRNA nuclear import was selective to certain tRNA species and may contribute to the changes in protein translation known to protect cells from stress. Keywords: tRNA, retrograde transport, nucleus, oxidative stress, fluorescence in situ hybridization, unfolded protein response, mTOR, REDD1, PKR |
url |
http://www.sciencedirect.com/science/article/pii/S2211124719302633 |
work_keys_str_mv |
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