On the role of magnesium ions in RNA stability

Divalent cations, like magnesium, are crucial for the structural integrity and biological activity of RNA. In this article, we present a picture of ho w magnesium stabilizes a particular folded Sonn of RNA. The overall stabili zation of RNA by Mg2+ is given by the free energy of transferring RNA from a reference univalent salt solution to a mired salt solution. This term has favorable energetic contributions Sr om two distinct modes of binding. dif fuse binding and site binding. In diffuse binding, fully hydrated Mg ions i nteract with the RNA via nonspecific long-range electrostatic interactions. In site binding, dehydrated Mg2+ interacts with anionic ligands specifical ly arranged by the RNA Sold to act as coordinating ligands for the metal io n. Each of these modes has a strong coulombic contribution to binding; howe ver, sire binding is also characterized by substantial changes in ion solva tion and other nonelectrostatic contributions. We will show how these energ etic differences can be exploited to experimentally. distinguish between th ese two classes Of ions rising analyses of binding polynomials. We survey a number of specific systems in which Mg2+-RNA interactions have been studie d In well-characterized systems such as certain tRNAs and some rRNA fragmen ts these studies show that site-bound ions can play an important role in RN A stability. However the crucial role of diffusely bound ions is also evide nt. We emphasize that diffuse binding can only be described rigorously by; a model that accounts for long-range electrostatic forces. To Sully underst and the role of magnesium ions in RNA stability, theoretical models describ ing electrostatic forces in systems with complicated structures must be dev eloped. (C) 1999 John Wiley & Sons, Inc.