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
Affiliations
Maria Vera
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States; Département de Biologie du Développement et Cellules Souches, Institut Pasteur, CNRS URA2578, Paris, France; Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, United States; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, New York, United States
Bibhusita Pani
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States
Lowri A Griffiths
Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom
Christian Muchardt
Département de Biologie du Développement et Cellules Souches, Institut Pasteur, CNRS URA2578, Paris, France
Catherine M Abbott
Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom
Robert H Singer
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, United States; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, New York, United States
Evgeny Nudler
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States; Howard Hughes Medical Institute, New York University School of Medicine, New York, United States
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.
