The heat shock response is important in eukaryotes as a protective mechanism for the stress of change in temperature or other environmental factors, and it has been the subject for targets for therapeutic intervention. Recently, it has been found that a conserved non-coding RNA is involved in mediating the heat shock response. The RNA forms a stable complex with elongation factor eEF1A to activate the heat shock transcription factor. The project will involve the preparation of recombinant RNA-protein complex for structural elucidation by X-ray crystallography and biochemical and biophysical characterisation. The structural information may help to explain how the RNA triggers the response, most likely through a conformational switch. Currently there is no structural information available for the heat shock RNA or for any of the several other large non-coding RNAs that have recently been identified in eukaryotes. The structural information may help to explain how the heat shock RNA and other non-coding RNAs function, and may also be useful in the long term for therapeutic intervention in response to chemotherapy of cancerous cells.
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