Cargando…

The translation elongation factor eEF1A1 couples transcription to translation during heat shock response

Translation elongation factor eEF1A has a well-defined role in protein synthesis. In this study, we demonstrate a new role for eEF1A: it participates in the entire process of the heat shock response (HSR) in mammalian cells from transcription through translation. Upon stress, isoform 1 of eEF1A rapi...

Descripción completa

Detalles Bibliográficos
Autores principales: Vera, Maria, Pani, Bibhusita, Griffiths, Lowri A, Muchardt, Christian, Abbott, Catherine M, Singer, Robert H, Nudler, Evgeny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164936/
https://www.ncbi.nlm.nih.gov/pubmed/25233275
http://dx.doi.org/10.7554/eLife.03164
_version_ 1782335032119001088
author Vera, Maria
Pani, Bibhusita
Griffiths, Lowri A
Muchardt, Christian
Abbott, Catherine M
Singer, Robert H
Nudler, Evgeny
author_facet Vera, Maria
Pani, Bibhusita
Griffiths, Lowri A
Muchardt, Christian
Abbott, Catherine M
Singer, Robert H
Nudler, Evgeny
author_sort Vera, Maria
collection PubMed
description Translation elongation factor eEF1A has a well-defined role in protein synthesis. In this study, we demonstrate a new role for eEF1A: it participates in the entire process of the heat shock response (HSR) in mammalian cells from transcription through translation. Upon stress, isoform 1 of eEF1A rapidly activates transcription of HSP70 by recruiting the master regulator HSF1 to its promoter. eEF1A1 then associates with elongating RNA polymerase II and the 3′UTR of HSP70 mRNA, stabilizing it and facilitating its transport from the nucleus to active ribosomes. eEF1A1-depleted cells exhibit severely impaired HSR and compromised thermotolerance. In contrast, tissue-specific isoform 2 of eEF1A does not support HSR. By adjusting transcriptional yield to translational needs, eEF1A1 renders HSR rapid, robust, and highly selective; thus, representing an attractive therapeutic target for numerous conditions associated with disrupted protein homeostasis, ranging from neurodegeneration to cancer. DOI: http://dx.doi.org/10.7554/eLife.03164.001
format Online
Article
Text
id pubmed-4164936
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-41649362014-10-17 The translation elongation factor eEF1A1 couples transcription to translation during heat shock response Vera, Maria Pani, Bibhusita Griffiths, Lowri A Muchardt, Christian Abbott, Catherine M Singer, Robert H Nudler, Evgeny eLife Biochemistry Translation elongation factor eEF1A has a well-defined role in protein synthesis. In this study, we demonstrate a new role for eEF1A: it participates in the entire process of the heat shock response (HSR) in mammalian cells from transcription through translation. Upon stress, isoform 1 of eEF1A rapidly activates transcription of HSP70 by recruiting the master regulator HSF1 to its promoter. eEF1A1 then associates with elongating RNA polymerase II and the 3′UTR of HSP70 mRNA, stabilizing it and facilitating its transport from the nucleus to active ribosomes. eEF1A1-depleted cells exhibit severely impaired HSR and compromised thermotolerance. In contrast, tissue-specific isoform 2 of eEF1A does not support HSR. By adjusting transcriptional yield to translational needs, eEF1A1 renders HSR rapid, robust, and highly selective; thus, representing an attractive therapeutic target for numerous conditions associated with disrupted protein homeostasis, ranging from neurodegeneration to cancer. DOI: http://dx.doi.org/10.7554/eLife.03164.001 eLife Sciences Publications, Ltd 2014-09-16 /pmc/articles/PMC4164936/ /pubmed/25233275 http://dx.doi.org/10.7554/eLife.03164 Text en Copyright © 2014, Vera et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry
Vera, Maria
Pani, Bibhusita
Griffiths, Lowri A
Muchardt, Christian
Abbott, Catherine M
Singer, Robert H
Nudler, Evgeny
The translation elongation factor eEF1A1 couples transcription to translation during heat shock response
title The translation elongation factor eEF1A1 couples transcription to translation during heat shock response
title_full The translation elongation factor eEF1A1 couples transcription to translation during heat shock response
title_fullStr The translation elongation factor eEF1A1 couples transcription to translation during heat shock response
title_full_unstemmed The translation elongation factor eEF1A1 couples transcription to translation during heat shock response
title_short The translation elongation factor eEF1A1 couples transcription to translation during heat shock response
title_sort translation elongation factor eef1a1 couples transcription to translation during heat shock response
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164936/
https://www.ncbi.nlm.nih.gov/pubmed/25233275
http://dx.doi.org/10.7554/eLife.03164
work_keys_str_mv AT veramaria thetranslationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT panibibhusita thetranslationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT griffithslowria thetranslationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT muchardtchristian thetranslationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT abbottcatherinem thetranslationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT singerroberth thetranslationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT nudlerevgeny thetranslationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT veramaria translationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT panibibhusita translationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT griffithslowria translationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT muchardtchristian translationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT abbottcatherinem translationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT singerroberth translationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse
AT nudlerevgeny translationelongationfactoreef1a1couplestranscriptiontotranslationduringheatshockresponse