Thermodynamic Origins
of Monovalent Facilitated RNA
Folding
- Publication date
- Publisher
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
(Δ<i>G</i>°), enthalpy (Δ<i>H</i>°), and entropy (Δ<i>S</i>°) of folding
for an isolated tetraloop–receptor tertiary interaction as
a function of Na<sup>+</sup> concentration. Somewhat unexpectedly,
increasing the Na<sup>+</sup> concentration changes the folding enthalpy
from a strongly exothermic process [e.g., Δ<i>H</i>° = −26(2) kcal/mol at 180 mM] to a weakly exothermic
process [e.g., Δ<i>H</i>° = −4(1) kcal/mol
at 630 mM]. As a direct corollary, it is the strong increase in folding
entropy [Δ(Δ<i>S</i>°) > 0] that compensates
for this loss of exothermicity for the achievement of more favorable
folding [Δ(Δ<i>G</i>°) < 0] at higher
Na<sup>+</sup> 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<sup>+</sup> 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