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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Main Authors: Hagen Schwenzer, Frank Jühling, Alexander Chu, Laura J. Pallett, Thomas F. Baumert, Mala Maini, Ariberto Fassati
Format: Article
Language:English
Published: Elsevier 2019-03-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124719302633
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spelling 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
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