Biology subjects

MAITY, H.

Publications and source records attributed to MAITY, H..

3 recordsLinked to original sources

bioRxiv2025

Temperature-Dependent Ion Migration Underlies Sequence-Specific RNA Collapse

Ions and temperature jointly regulate RNA structure, dynamics and phase behavior, yet their coupled effects remain poorly understood at the molecular level. Single-stranded RNA (ssRNA), a ubiquitous and functionally versatile class of RNA, presents a particularly challenging target due to its intrinsic flexibility and pronounced sensitivity to ionic and thermal perturbations. Here, we extend our previously validated coarse-grained RNA model by introducing temperature-dependent divalent ion-phosphate potentials along with revised stacking interactions to elucidate how electrostatics, stacking, and hydration collectively determine ssRNA behavior. Our simulations quantitatively reproduce experimental SAXS profiles across a broad range of ionic conditions and reveal a non-monotonic temperature dependence of RNA compaction: ssRNAs expand upon heating, reach a sequence-specific maximum size, and then collapse as enhanced counterion condensation dominates. Rising temperature strengthens ion-RNA interactions, leading to a reorganization from diffusive to inner-sphere coordination, directly linking RNA collapse to ion dehydration. Our results establish that the ion atmosphere is a dynamic, sequence-encoded extension of RNA structure. This framework provides molecular insight into how temperature and ions govern RNA conformational transitions, offering a microscopic basis for RNA thermoadaptation, cold-induced misfolding, and RNA phase transitions. Statement of SignificanceIons and temperature strongly influence RNA structure and dynamics, yet the molecular mechanisms by which these factors jointly regulate RNA behavior remain poorly understood. Using coarse-grained simulations with temperature-dependent Mg2+-phosphate interactions, we report how ion binding reorganizes around single-stranded RNAs as temperature increases. We found that unstructured RNAs undergo a non-monotonic structural transition: thermal disruption of base stacking first expands the chain, followed by the collapse driven by enhanced Mg2+ binding. This collapse arises from a temperature-induced migration of Mg2+ from diffusive ion atmosphere to direct inner-sphere binding, linking RNA compaction to ion dehydration and entropy-driven binding. These results reveal that the RNA ion atmosphere is a dynamic, structure-coupled component of RNA organization and provide a mechanistic basis for thermoresponsive RNA condensation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/683600v3_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@fe79beorg.highwire.dtl.DTLVardef@eaac88org.highwire.dtl.DTLVardef@e52bc1org.highwire.dtl.DTLVardef@19bbea0_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2025

RNA structural complexity dictates its ion atmosphere

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

biophysics↗

bioRxiv2023

Salt-dependent self-association of trinucleotide repeat RNA sequences

Low complexity repeat RNA sequences self-associate by homotypic interactions to form condensates. Using simulations of a coarse grained Single-Interaction Site model for (CAG)n (n = 30 and 31), we show that the salt-dependent free energy gap, {triangleup}GS, between the ground (perfect hairpin) and the excited state (slipped hairpin (SH) with one CAG overhang) of monomer (n even) is the primary factor that determines the rates and yield of self-assembly. For odd n, the SH ground state free energy (GS) is used to predict self-association kinetics. As the monovalent salt concentration, CS, increases {triangleup}GS and GS increases, which in turn decreases the self-association rates. In contrast, {triangleup}GS for scrambled sequences, with the same length and sequence composition as (CAG)31 but with higher complexity, is larger which greatly suppresses the propensities to aggregate. Although demonstrated explicitly for (CAG)30 and (CAG)31 polymers, the finding that there is an inverse correlation between CS-dependent {triangleup}GS or GS and RNA aggregation is general. Our predictions are amenable to experimental tests.

biophysics↗