title: The translation elongation factor eEF1A1 couples transcription to translation during heat shock response.
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.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States.
authors.forename: Maria
authors.initials: M
authors.lastname: Vera
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States.
authors.forename: Bibhusita
authors.initials: B
authors.lastname: Pani
authors.affiliation: Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Lowri A
authors.initials: LA
authors.lastname: Griffiths
authors.affiliation: Département de Biologie du Développement et Cellules Souches, Institut Pasteur, CNRS URA2578, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Muchardt
authors.affiliation: Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Abbott
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, United States.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Singer
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Nudler
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008856:Microscopy, Fluorescence; D020648:Peptide Elongation Factor 1 / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D014176:Protein Biosynthesis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C094814:EEF1A1 protein, human; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D020648:Peptide Elongation Factor 1; D014157:Transcription Factors
keywords: RNA stability; biochemistry; cell biology; human; mouse; nuclear export; transcription factors