On the role of magnesium ions in RNA stability

Abstract

Divalent cations, like magnesium, are crucial for the structural integrity and biological activity of RNA. In this article, we present a picture of how magnesium stabilizes a particular folded form of RNA. The overall stabilization of RNA by Mg2+ is given by the free energy of transferring RNA from a reference univalent salt solution to a mixed salt solution. This term has favorable energetic contributions from two distinct modes of binding: diffuse binding and site binding. In diffuse binding, fully hydrated Mg ions interact with the RNA via nonspecific long‐range electrostatic interactions. In site binding, dehydrated Mg2+ interacts with anionic ligands specifically arranged by the RNA fold to act as coordinating ligands for the metal ion. Each of these modes has a strong coulombic contribution to binding; however, site binding is also characterized by substantial changes in ion solvation and other nonelectrostatic contributions. We will show how these energetic differences can be exploited to experimentally distinguish between these two classes of ions using analyses of binding polynomials. We survey a number of specific systems in which Mg2+–RNA interactions have been studied. In well‐characterized systems such as certain tRNAs and some rRNA fragments these studies show that site‐bound ions can play an important role in RNA stability. However, the crucial role of diffusely bound ions is also evident. We emphasize that diffuse binding can only be described rigorously by a model that accounts for long‐range electrostatic forces. To fully understand the role of magnesium ions in RNA stability, theoretical models describing electrostatic forces in systems with complicated structures must be developed. © 1999 John Wiley & Sons, Inc. Biopoly 48: 113–135, 1998

Metal‐Induced Specific and Nonspecific Oligonucleotide Folding Studied by FRET and Related Biophysical and Bioanalytical Implications

“…They can either specifically coordinate with nucleic acids or through diffuse binding. [38] Overall a similar pattern was observed as shown in Figure 4A, D; Hg II can still be detected under all of the tested conditions. As shown in Figure 4B, E, the sensitivity became higher with an increasing concentration of these metal ions.…”

Dissociation of Intact Escherichia coli Ribosomes in a Mass Spectrometer

“…From the spectra recorded under these solution conditions, we can conclude that Mg 2ϩ ions are replaced partially by Li ϩ and that as a result of this cation exchange only a subset of proteins remains firmly attached to the RNA scaffold in the gas phase. It is well established that Mg 2ϩ is crucial for the structural integrity of RNA interacting either by diffuse binding in which fully hydrated Mg 2ϩ binds to RNA via nonspecific long range electrostatic interactions or by site-specific interactions with anionic ligands facilitated by the RNA fold (29). The binding of Mg 2ϩ to the acidic stalk proteins observed in the present study is presumably nonspecific, because multiple adducts are observed, and demonstrates the presence of the diffuse Mg 2ϩ cloud surrounding rRNA.…”

Predicting Stability of DNA Duplexes in Solutions Containing Magnesium and Monovalent Cations

“…Both divalent and monovalent cations bind to nucleic acid molecules and affect their physical properties (1). Magnesium cations stabilize nucleic acid duplexes and facilitate their folding into secondary and tertiary structures (2), which are biologically active. Mg 2+ ions are also necessary cofactors of many enzymatic reactions involving nucleic acids (3).…”