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

Maria Vera Ugalde, Bibhusita Pani, Lowri A. Griffiths, Christian Muchardt, Catherine M. Abbott, Robert H. Singer, Evgeny Nudler

Research output: Contribution to journalArticle

49 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)e03164
JournaleLife
Volume3
DOIs
StatePublished - 2014

Fingerprint

Peptide Elongation Factors
Heat-Shock Response
Transcription
Protein Isoforms
RNA Polymerase II
3' Untranslated Regions
Ribosomes
Proteins
Homeostasis
Cells
Tissue
Messenger RNA
Hot Temperature
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Vera Ugalde, M., Pani, B., Griffiths, L. A., Muchardt, C., Abbott, C. M., Singer, R. H., & Nudler, E. (2014). The translation elongation factor eEF1A1 couples transcription to translation during heat shock response. eLife, 3, e03164. https://doi.org/10.7554/eLife.03164

The translation elongation factor eEF1A1 couples transcription to translation during heat shock response. / Vera Ugalde, Maria; Pani, Bibhusita; Griffiths, Lowri A.; Muchardt, Christian; Abbott, Catherine M.; Singer, Robert H.; Nudler, Evgeny.

In: eLife, Vol. 3, 2014, p. e03164.

Research output: Contribution to journalArticle

Vera Ugalde, M, Pani, B, Griffiths, LA, Muchardt, C, Abbott, CM, Singer, RH & Nudler, E 2014, 'The translation elongation factor eEF1A1 couples transcription to translation during heat shock response', eLife, vol. 3, pp. e03164. https://doi.org/10.7554/eLife.03164
Vera Ugalde, 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. In: eLife. 2014 ; Vol. 3. pp. e03164.
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