title: Kinetic intermediates in RNA folding.
abstract: The folding pathways of large, highly structured RNA molecules are largely unexplored. Insight into both the kinetics of folding and the presence of intermediates was provided in a study of the Mg(2+)-induced folding of the Tetrahymena ribozyme by hybridization of complementary oligodeoxynucleotide probes. This RNA folds via a complex mechanism involving both Mg(2+)-dependent and Mg(2+)-independent steps. A hierarchical model for the folding pathway is proposed in which formation of one helical domain (P4-P6) precedes that of a second helical domain (P3-P7). The overall rate-limiting step is formation of P3-P7, and takes place with an observed rate constant of 0.72 +/- 0.14 minute-1. The folding mechanism of large RNAs appears similar to that of many multidomain proteins in that formation of independently stable substructures precedes their association into the final conformation.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: P P
authors.initials: PP
authors.lastname: Zarrinkar
authors.forename: J R
authors.initials: JR
authors.lastname: Williamson
mesh_terms: D000818:Animals; D001483:Base Sequence; D007438:Introns; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D016337:RNA, Catalytic / Q000737:chemistry* / Q000378:metabolism; D016053:RNA, Protozoan / Q000737:chemistry*; D016914:Ribonuclease H / Q000378:metabolism; D013696:Temperature; D013768:Tetrahymena / Q000235:genetics*
chemical_list: D015345:Oligonucleotide Probes; D016337:RNA, Catalytic; D016053:RNA, Protozoan; D016914:Ribonuclease H; D008274:Magnesium