title: Protein folding activity of ribosomal RNA is a selective target of two unrelated antiprion drugs.
abstract: BACKGROUND
  6-Aminophenanthridine (6AP) and Guanabenz (GA, a drug currently in use for the treatment of hypertension) were isolated as antiprion drugs using a yeast-based assay. These structurally unrelated molecules are also active against mammalian prion in several cell-based assays and in vivo in a mouse model for prion-based diseases.
  
  
  RESULTS
  Here we report the identification of cellular targets of these drugs. Using affinity chromatography matrices for both drugs, we demonstrate an RNA-dependent interaction of 6AP and GA with the ribosome. These specific interactions have no effect on the peptidyl transferase activity of the ribosome or on global translation. In contrast, 6AP and GA specifically inhibit the ribosomal RNA-mediated protein folding activity of the ribosome.
  
  
  CONCLUSIONS
  6AP and GA are therefore the first compounds to selectively inhibit the protein folding activity of the ribosome. They thus constitute precious tools to study the yet largely unexplored biological role of this protein folding activity.
authors.affiliation: INSERM U613, Brest, France.
authors.forename: Déborah
authors.initials: D
authors.lastname: Tribouillard-Tanvier
authors.forename: Suzana
authors.initials: S
authors.lastname: Dos Reis
authors.forename: Fabienne
authors.initials: F
authors.lastname: Gug
authors.forename: Cécile
authors.initials: C
authors.lastname: Voisset
authors.forename: Vincent
authors.initials: V
authors.lastname: Béringue
authors.forename: Raimon
authors.initials: R
authors.lastname: Sabate
authors.forename: Ema
authors.initials: E
authors.lastname: Kikovska
authors.forename: Nicolas
authors.initials: N
authors.lastname: Talarek
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bach
authors.forename: Chenhui
authors.initials: C
authors.lastname: Huang
authors.forename: Nathalie
authors.initials: N
authors.lastname: Desban
authors.forename: Sven J
authors.initials: SJ
authors.lastname: Saupe
authors.forename: Surachai
authors.initials: S
authors.lastname: Supattapone
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Thuret
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chédin
authors.forename: Didier
authors.initials: D
authors.lastname: Vilette
authors.forename: Hervé
authors.initials: H
authors.lastname: Galons
authors.forename: Suparna
authors.initials: S
authors.lastname: Sanyal
authors.forename: Marc
authors.initials: M
authors.lastname: Blondel
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D002846:Chromatography, Affinity; D004591:Electrophoresis, Polyacrylamide Gel; D006143:Guanabenz / Q000494:pharmacology*; D011328:Prions / Q000187:drug effects*; D017510:Protein Folding; D012335:RNA, Ribosomal / Q000187:drug effects / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D011328:Prions; D012335:RNA, Ribosomal; D006143:Guanabenz