title: Charge density of divalent metal cations determines RNA stability.
abstract: RNA molecules are exquisitely sensitive to the properties of counterions. The folding equilibrium of the Tetrahymena ribozyme is measured by nondenaturing gel electrophoresis in the presence of divalent group IIA metal cations. The stability of the folded ribozyme increases with the charge density (zeta) of the cation. Similar scaling is found when the free energy of the RNA folded in small and large metal cations is measured by urea denaturation. Brownian dynamics simulations of a polyelectrolyte show that the experimental observations can be explained by nonspecific ion-RNA interactions in the absence of site-specific metal chelation. The experimental and simulation results establish that RNA stability is largely determined by a combination of counterion charge and the packing efficiency of condensed cations that depends on the excluded volume of the cations.
authors.affiliation: T. C. Jenkins Department of Biophysics, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Eda
authors.initials: E
authors.lastname: Koculi
authors.forename: Changbong
authors.initials: C
authors.lastname: Hyeon
authors.forename: D
authors.initials: D
authors.lastname: Thirumalai
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Woodson
mesh_terms: D000818:Animals; D001665:Binding Sites; D002413:Cations, Divalent / Q000494:pharmacology; D003198:Computer Simulation; D004573:Electrolytes / Q000737:chemistry; D004586:Electrophoresis; D019277:Entropy; D008670:Metals / Q000494:pharmacology*; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D012313:RNA / Q000737:chemistry*; D020871:RNA Stability / Q000187:drug effects*; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D013768:Tetrahymena / Q000235:genetics / Q000378:metabolism; D014508:Urea / Q000494:pharmacology
chemical_list: D002413:Cations, Divalent; D004573:Electrolytes; D008670:Metals; D016337:RNA, Catalytic; D012313:RNA; D014508:Urea