Understanding the Thermodynamics of Magnesium Binding to RNA Structural Motifs

Divalent magnesium ions (Mg²⁺) serve a vital role in defining the structural and catalytic chemistry of a wide array of RNA molecules. The body of structural information on RNA motifs continues to expand and, in turn, the functional importance of Mg²⁺ is revealed. A combination of prior work on the structural characterization of magnesium binding ligands with inner- and outer-sphere coordination modes, with recorded experimental binding energies for inner- and outer-sphere contacts, demonstrates the relative affinity and thermodynamic hierarchy for these sites. In turn, these can be correlated with cellular concentrations of free available magnesium ions, allowing the prioritization of populating important functional sites and a correlation with physiological function. This paper summarizes some of the key results of that analysis and provides predictive rules for the affinity and role of newly identified Mg binding sites on complex RNA structures. The influence of crystal packing on magnesium binding to RNA motifs, relative to their solution form, is addressed and caveats made.