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

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

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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)
Article numbere03164
Pages (from-to)e03164
JournaleLife
Volume3
DOIs
StatePublished - 2014

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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