title: Inhibition by polyamines of the hammerhead ribozyme from a Chrysanthemum chlorotic mottle viroid.
abstract: BACKGROUND
  Viroids are the smallest pathogens known to date. They infect plants and cause considerable economic losses. The members of the Avsunviroidae family are known for their capability to form hammerhead ribozymes (HHR) that catalyze self-cleavage during their rolling circle replication.
  
  
  METHODS
  In vitro inhibition assays, based on the self-cleavage kinetics of the hammerhead ribozyme from a Chrysanthemum chlorotic mottle viroid (CChMVd-HHR) were performed in the presence of various putative inhibitors.
  
  
  RESULTS
  Aminated compounds appear to be inhibitors of the self-cleavage activity of the CChMVd HHR. Surprisingly the spermine, a known activator of the autocatalytic activity of another hammerhead ribozyme in the presence or absence of divalent cations, is a potent inhibitor of the CChMVd-HHR with Ki of 17±5μM. Ruthenium hexamine and TMPyP4 are also efficient inhibitors with Ki of 32±5μM and IC50 of 177±5nM, respectively.
  
  
  CONCLUSIONS
  This study shows that polyamines are inhibitors of the CChMVd-HHR self-cleavage activity, with an efficiency that increases with the number of their amino groups.
  
  
  CONCLUSIONS
  This fundamental investigation is of interest in understanding the catalytic activity of HHR as it is now known that HHR are present in the three domains of life including in the human genome. In addition these results emphasize again the remarkable plasticity and adaptability of ribozymes, a property which might have played a role in the early developments of life and must be also of significance nowadays for the multiple functions played by non-coding RNAs.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 7205, F-75005 Paris, France.
authors.forename: Hussein
authors.initials: H
authors.lastname: Kaddour
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 7205, F-75005 Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Vergne
authors.affiliation: Laboratoire BIOSIPE, CNRS, ER3 UPMC Université Paris 06, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Herve
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 7205, F-75005 Paris, France. Electronic address: marie-christine.maurel@upmc.fr.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Maurel
mesh_terms: D031202:Chrysanthemum / Q000821:virology*; D003035:Cobalt / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology; D016337:RNA, Catalytic / Q000037:antagonists & inhibitors* / Q000502:physiology; D017975:Ruthenium Compounds / Q000494:pharmacology; D014772:Viroids / Q000502:physiology*
chemical_list: D011073:Polyamines; D011166:Porphyrins; D016337:RNA, Catalytic; D017975:Ruthenium Compounds; C427204:hammerhead ribozyme; C032300:hexaamminecobalt(II); C031584:hexammineruthenium; C021096:tetra(4-N-methylpyridyl)porphine; D003035:Cobalt
keywords: Chrysanthemum; Polyamine; RNA; Ribozyme; Viroid