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bioRxiv · 10.1101/2025.05.19.654961

RNA structural complexity dictates its ion atmosphere

MAITY, H.·Zhang, P.·Thirumalai, D.·Nguyen, H. T.
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Abstract

Electrostatic interactions mediated by the surrounding ions govern virtually every facet of RNA behavior. Most studies have focused on rigid, well-folded motifs, leaving the structurally heteregeneous, and biologically ubiquitous, flexible RNAs underexplored. To address this gap, we performed molecular dynamics simulation of three RNAs spanning the structural continuum: an unstructured poly-uridylic tract (rU30), a semiflexible cytosine-adenine-guanine (CAG) repeat, and the tightly folded Beet Western Yellow Virus (BWYV) pseudoknot. Despite carrying nearly identical net charge, their ion atmospheres diverge strikingly. rU30 envelops itself in a diffuse Mg2+ environment retained through two or more hydration shells, whereas the CAG repeat and pseudoknot favor more localized outer-sphere Mg2+ binding. In contrast, Ca2+ tends to form inner-sphere contacts with all three RNAs, regardless of their folds. Remarkably, the diffuse ion clouds around unstructured RNAs extend farther into solution than that of the folded RNAs, significantly broadening their electrostatic sphere of influence. Nonetheless, the ion exchange kinetics remain virtually unchanged, demonstrating a surprising decoupling between spatial distribution and dynamical turnover. Our findings reveal RNA structural flexibility as a powerful lever for tuning ionic screening, with important implications for biomolecular recognition, RNA-driven phase separation, and physical properties of RNA-rich condensate. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/654961v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@12e78aborg.highwire.dtl.DTLVardef@1f4328borg.highwire.dtl.DTLVardef@122561dorg.highwire.dtl.DTLVardef@143c5ff_HPS_FORMAT_FIGEXP M_FIG C_FIG

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MAITY, H., Zhang, P., Thirumalai, D., Nguyen, H. T.. 2025-05-21. RNA structural complexity dictates its ion atmosphere. https://doi.org/10.1101/2025.05.19.654961

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