Thermodynamic origins of monovalent facilitated RNA folding.

ABSTRACT: Cations have long been associated with formation of native RNA structure and are commonly thought to stabilize the formation of tertiary contacts by favorably interacting with the electrostatic potential of the RNA, giving rise to an "ion atmosphere". A significant amount of information regarding the thermodynamics of structural transitions in the presence of an ion atmosphere has accumulated and suggests stabilization is dominated by entropic terms. This work provides an analysis of how RNA-cation interactions affect the entropy and enthalpy associated with an RNA tertiary transition. Specifically, temperature-dependent single-molecule fluorescence resonance energy transfer studies have been exploited to determine the free energy (?G°), enthalpy (?H°), and entropy (?S°) of folding for an isolated tetraloop-receptor tertiary interaction as a function of Na(+) concentration. Somewhat unexpectedly, increasing the Na(+) concentration changes the folding enthalpy from a strongly exothermic process [e.g., ?H° = -26(2) kcal/mol at 180 mM] to a weakly exothermic process [e.g., ?H° = -4(1) kcal/mol at 630 mM]. As a direct corollary, it is the strong increase in folding entropy [?(?S°) > 0] that compensates for this loss of exothermicity for the achievement of more favorable folding [?(?G°) < 0] at higher Na(+) concentrations. In conjunction with corresponding measurements of the thermodynamics of the transition state barrier, these data provide a detailed description of the folding pathway associated with the GAAA tetraloop-receptor interaction as a function of Na(+) concentration. The results support a potentially universal mechanism for monovalent facilitated RNA folding, whereby an increasing monovalent concentration stabilizes tertiary structure by reducing the entropic penalty for folding.

SUBMITTER: Holmstrom ED 

PROVIDER: S-EPMC3366770 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature