The heat-shock transcription factor 1 (HSF1) has an important role in the heat-shock response in vertebrates by inducing the expression of heat-shock proteins (HSPs) and other cytoprotective proteins¹. HSF1 is present in unstressed cells in an inactive monomeric form and becomes activated by heat and other stress stimuli. HSF1 activation involves trimerization and acquisition of a site-specific DNA-binding activity^{2, 3}, which is negatively regulated by interaction with certain HSPs^{4, 5, 6}. Here we show that HSF1 activation by heat shock is an active process that is mediated by a ribonucleoprotein complex containing translation elongation factor eEF1A and a previously unknown non-coding RNA that we term HSR1 (heat shock RNA-1). HSR1 is constitutively expressed in human and rodent cells and its homologues are functionally interchangeable. Both HSR1 and eEF1A are required for HSF1 activation in vitro; antisense oligonucleotides or short interfering (si)RNA against HSR1 impair the heat-shock response in vivo, rendering cells thermosensitive. The central role of HSR1 during heat shock implies that targeting this RNA could serve as a new therapeutic model for cancer, inflammation and other conditions associated with HSF1 deregulation.

1. Department of Biochemistry, New York University School of Medicine, New York, New York 10016, USA
2. Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel
3. The Cleveland Clinic Foundation Lerner Research Institute, Cleveland, Ohio 44195, USA
4. Redox Pharmaceutical Corp, Greenvale, New York 11548, USA

Correspondence to: David Gershon^2,4Evgeny Nudler¹ Correspondence and requests for materials should be addressed to E.N. (Email: evgeny.nudler@med.nyu.edu) or D.G. (Email: dgershon@redoxpharm.com).

Received 31 August 2005 | Accepted 15 December 2005

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