Structural Biochemistry/Salt Effects on Mechanical Folding

With one negative charge per connective phosphate, RNA is considered a polyelectrolyte. In order to achieve neutrality, RNA attracts cations, creating a counterion atmosphere. While weak, this cation bonding is crucial to maintain both secondary and tertiary structures. For this reason, the structure, stability, and reactivity are heavily dependent on external ionic conditions. Salt, usually in the form of Mg(2+), has been found to have profound kinetic effects on the folded and unfolded states of RNA (Li, Vieregg, Tinoco Jr, 85). The addition of salt causes a higher kinetic barrier between the folded and unfolded states, but does not effect the point at which the transition between the two states occurs.

The aforementioned statement was confirmed by a study by Li, Vieregg, and Tinoco Jr titled "How RNA Unfolds and Refolds." The study examined the effect of increasing levels of Mg(2+) on RNA hairpins and a three-helix junction. As predicted, the addition of the salt resulted in higher energy unfolding and refolding, meaning that the higher concentration of cations stabilizes secondary structures. This increase in stability was found to be the result of a slight decrease in the unfolding rate and a larger increase in the folding rate of the RNA (87). Monovalent cations were also studied, and where found to have the same effect as divalent salts, but to a much lesser extent (86).

Metal ions, like Mg(2+), have an even stronger effect on RNA tertiary structure than on secondary structure, due to a higher dependence on ionic conditions. The addition of metal ions greatly slows the process of undoing tertiary structure, but has little effect on tertiary folding rates (88). For example, loop-loop interactions, which rely on a "kissing" interaction, becomes highly stabilized with the addition on a mere mM of Mg(2+).


Li, Pan T.X., Jeffrey Vieregg, and Ignacio Tinoco. "How RNA Unfolds and Refolds." Annual Review of Biochemistry 77.1 (2008): 77-100. Print.