title: An RNA aptamer perturbs heat shock transcription factor activity in Drosophila melanogaster.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: H Hans
authors.initials: HH
authors.lastname: Salamanca
authors.forename: Nicholas
authors.initials: N
authors.lastname: Fuda
authors.forename: Hua
authors.initials: H
authors.lastname: Shi
authors.forename: John T
authors.initials: JT
authors.lastname: Lis
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response; D020935:MAP Kinase Signaling System / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D052157:Aptamers, Nucleotide; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C089272:Hsp83 protein, Drosophila; D014157:Transcription Factors