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RNA-mediated response to heat shock in mammalian cells

Nature volume 440, pages 556–560 (2006)Cite this article

Abstract

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 activity2,3, which is negatively regulated by interaction with certain HSPs4,5,6. 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.

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Figure 1: Identification of an HSF1-activating fraction containing eEF1A.
Figure 2: HSR1-mediated activation of HSF1.
Figure 3: Inhibition of the heat-shock response in vivo by targeting HSR1.

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Acknowledgements

We thank M. Schick and E. Avetissova for technical assistance and N. J. Cowan for critical reading of the manuscript. This work was supported by grants from the NIH and the Edward Mallinckrodt Jr Foundation (E.N.).

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Authors and Affiliations

  1. Department of Biochemistry, New York University School of Medicine, New York, 10016, New York, USA

    Ilya Shamovsky, Maxim Ivannikov & Evgeny Nudler

  2. Faculty of Biology, Technion-Israel Institute of Technology, 32000, Haifa, Israel

    Ilya Shamovsky & David Gershon

  3. The Cleveland Clinic Foundation Lerner Research Institute, Ohio, 44195, Cleveland, USA

    Eugene S. Kandel

  4. Redox Pharmaceutical Corp, New York, 11548, Greenvale, USA

    David Gershon

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  1. Ilya Shamovsky
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Correspondence to David Gershon or Evgeny Nudler.

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Shamovsky, I., Ivannikov, M., Kandel, E. et al. RNA-mediated response to heat shock in mammalian cells. Nature 440, 556–560 (2006). https://doi.org/10.1038/nature04518

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