Role of Cations in RNA Folding and Function

Inorganic cations and their hydrates are essential for life on Earth. Water molecules are oriented and polarized by cations, forming acidic metal hydrates with increased potential for participation in hydrogen bonding function in enzymatic activity and proton donation. Cations associate with RNA through a continuum of interactions, from neutralization of net charge to first-shell coordination of backbone phosphates. Cation coordination by RNA alters geometry of the hydrated cation and the structure of the RNA. The earliest available data suggests that the ribosome large subunit of the Last Universal Common Ancestor originated and has continued to evolve, with dependence on Mg²⁺ for folding of long, complex ribosomal RNA (rRNA), giving indirect support to catalysis of peptide bond formation. The phosphodiester backbone of rRNA is a frequent, though not exclusive, site of Mg²⁺ interaction. Two specific geometries of Mg²⁺-phosphodiester complexes support local and long-range interactions, including an intricate intra- and inter-domain network of interactions. Other natural ribozymes, in contrast, tolerate folding and function with a broader range of cations, perhaps from evolutionary necessity.