Poster abstracts

Poster number 97 submitted by Peter Zhang

Ion-dependent structural ensemble and phase separation propensity of single-stranded RNA

Heyang Zhang (Department of Chemistry, University at Buffalo), Hung T. Nguyen (Department of Chemistry, University at Buffalo)

Abstract:
Single-stranded RNAs (ssRNA) play important roles in many physiological processes, one of which is regulating molecular recognition in biomolecular condensates. Despite having only four simple building blocks, ssRNA adopts a complex array of structures, often with the help of counterions, hindering structural characterization by conventional experimental and theoretical techniques. To faithfully capture the structural ensemble of ssRNA, we optimized our coarse-grained RNA model, in which each nucleotide is represented by three interaction sites and interactions between RNA and Mg2+ ions are modeled with liquid-based integral equation theory. We adjusted stacking interactions between two consecutive nucleotides along the RNA chain, which are essential for RNA folding and structure prediction, to reproduce thermodynamics as described by the nearest-neighbor model. The updated model captures the structural ensemble of ssRNA homopolymers (rA30 and rU30), reproducing known experimental results such as radii of gyration, small angle X-ray scattering profiles, and ion counting experiments. We demonstrated that ssRNA homopolymers, unlike well-folded RNA, primarily binds to diffusive Mg2+. Additionally, we showed that ssRNA forms biomolecular condensates in the presence of Mg2+, driven primarily by electrostatic interactions. Our model provides a comprehensive treatment of ion-RNA interactions in terms of both energetic and structural features, allowing us to study ion-dependent RNA folding and phase separation.

References:
1. Maity, H., Zhang, H., Thirumalai, D. & Nguyen, H. T. RNA Structural Complexity Dictates Its Ion Atmosphere. J. Phys. Chem. Lett. 8393–8402 (2025) doi:10.1021/acs.jpclett.5c01656.

Keywords: RNA Structure, Computational Chemistry, RNA Magnesium Interactions