An RNA aptamer perturbs heat shock transcription factor activity in Drosophila melanogaster

Heat shock transcription factor (HSF1) is a conserved master regulator that orchestrates the protection of normal cells from stress. However, HSF1 also protects abnormal cells and is required for carcinogenesis. Here, we generate an highly specific RNA aptamer (iaRNA(HSF1)) that binds Drosophila HSF...

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Bibliographic Details
Published in:Nucleic acids research 2011-08, Vol.39 (15), p.6729-6740
Main Authors: Salamanca, H Hans, Fuda, Nicholas, Shi, Hua, Lis, John T
Format: Article
Language:English
Subjects:
Animals
Aptamers, Nucleotide - chemistry
Aptamers, Nucleotide - metabolism
Base Sequence
Cells, Cultured
DNA-Binding Proteins - antagonists & inhibitors
DNA-Binding Proteins - metabolism
Drosophila melanogaster
Drosophila melanogaster - genetics
Drosophila melanogaster - metabolism
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Heat Shock Transcription Factors
Heat-Shock Proteins - genetics
Heat-Shock Proteins - metabolism
Heat-Shock Response
MAP Kinase Signaling System - genetics
Molecular Sequence Data
Mutation
Phenotype
RNA
Transcription Factors - antagonists & inhibitors
Transcription Factors - metabolism
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Summary:Heat shock transcription factor (HSF1) is a conserved master regulator that orchestrates the protection of normal cells from stress. However, HSF1 also protects abnormal cells and is required for carcinogenesis. Here, we generate an highly specific RNA aptamer (iaRNA(HSF1)) that binds Drosophila HSF1 and inhibits HSF1 binding to DNA. In Drosophila animals, iaRNA(HSF1) reduces normal Hsp83 levels and promotes developmental abnormalities, mimicking the spectrum of phenotypes that occur when Hsp83 activity is reduced. The HSF1 aptamer also effectively suppresses the abnormal growth phenotypes induced by constitutively active forms of the EGF receptor and Raf oncoproteins. Our results indicate that HSF1 contributes toward the morphological development of animal traits by controlling the expression of molecular chaperones under normal growth conditions. Additionally, our study demonstrates the utility of the RNA aptamer technology as a promising chemical genetic approach to investigate biological mechanisms, including cancer and for identifying effective drug targets in vivo.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkr206