RT Journal Article
SR Electronic
T1 Ion Condensation onto Ribozyme is Site-Specific and Fold-Dependent
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 551994
DO 10.1101/551994
A1 Naoto Hori
A1 Natalia A. Denesyuk
A1 D. Thirumalai
YR 2019
UL http://biorxiv.org/content/early/2019/04/13/551994.abstract
AB The highly charged RNA molecules, with each phosphate carrying a single negative charge, cannot fold into well-defined architectures with tertiary interactions, in the absence of ions. For ribozymes, divalent cations are known to be more effcient than monovalent ions in driving them to a compact state although Mg2+ions are needed for catalytic activities. Therefore, how ions interact with RNA is relevant in understanding RNA folding. It is often thought that most of the ions are territorially and non-specifically bound to the RNA, as predicted by the counterion condensation (CIC) theory. Here, we show using simulations of Azoarcus ribozyme, based on an accurate coarse-grained Three Site Interaction (TIS) model, with explicit divalent and monovalent cations, that ion condensation is highly specific and depends on the nucleotide position. The regions with high coordination between the phosphate groups and the divalent cations are discernible even at very low Mg2+ concentrations when the ribozyme does not form tertiary interactions. Surprisingly, these regions also contain the secondary structural elements that nucleate subsequently in the self-assembly of RNA, implying that ion condensation is determined by the architecture of the folded state. These results are in sharp contrast to interactions of ions (monovalent and divalent) with rigid charged rods in which ion condensation is uniform and position independent. The differences are explained in terms of the dramatic non-monotonic shape fluctuations in the ribozyme as it folds with increasing Mg2+ or Ca2+ concentration.