Cation effects on the folding of ribosomal RNA
Lenz, Timothy Kenneth
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Folding of ribonucleic acids (RNAs), including those which constitute the functional components of the ribosome, invariably involves positively charged metal ions (cations). Here, we explore the intricate relationships between divalent cations and ribosomal structure, origins, and evolution. We develop and test a model of an ancestral ribosomal RNA which, despite extensive deletions, retains the ability to fold into its predicted secondary structure and associate specifically with Mg2+ ions. These results support that the functional core of the ribosome is an ancient assembly that has remained largely static over billions of years of evolution. We also find that modern protein-free ribosomal RNA exhibits widely-dispersed conformational changes upon association with Mg2+, consistent with global collapse to a near-native conformation containing many native tertiary interactions. By inference, the structural effects of ribosomal proteins are largely assumed to be local and nominal. We perform experiments designed to examine the structure of ribosomal RNA under plausible early earth conditions, particularly in presence of Fe2+, to study the emergence of the translation apparatus under relevant geochemical conditions. Our results suggest atomic-level mimicry of Fe2+ for Mg2+ in extant and ancient protein-free ribosomal RNA structures, both of which fold more readily in presence of Fe2+ than Mg2+. We discuss the observation of experimental patterns for certain RNA motifs, and the potential utility of these types of patterns in improving RNA structure prediction and validation.