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Elife. 2014 Sep 16;3:e03164. doi: 10.7554/eLife.03164.

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

Author information

1
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States.
2
Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom.
3
Département de Biologie du Développement et Cellules Souches, Institut Pasteur, CNRS URA2578, Paris, France.
4
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, United States.

Abstract

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.

KEYWORDS:

RNA stability; biochemistry; cell biology; human; mouse; nuclear export; transcription factors

PMID:
25233275
PMCID:
PMC4164936
DOI:
10.7554/eLife.03164
[Indexed for MEDLINE]
Free PMC Article

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