The Critical Role of the 2’-OH group in Phase Separation and Percolation Transitions of RNA

• DOI: 10.1101/2025.02.26.638501
• Publication Date: 2025-02-27T08:17:34Z
• Authors: Gable M. Wadsworth; Dilimulati Aierken; George M. Thurston; Jerelle A. Joseph; Priya R. Banerjee
• Keywords: Percolation (cognitive psychology); Separation (statistics)

Magnesium ion dependent RNA liquid-liquid phase separation with lower critical solution temperatures is driven by the phosphate backbone and modulated solvation property of nucleobases. Here, we report a key role 2'-OH group ribose sugar in condensation presence divalent cations. We show that 2'-deoxyribose inhibits nucleic acid suppresses intra-condensate networking transition, known as percolation, underlies condensate dynamical arrest. All-atom simulations reveal increased compaction single-stranded DNA compared to RNA, suggesting an unintuitive chain flexibility modulating heat induced percolation transitions. Further, 2'-O-methylation (2'-O-Me) common modification, lowers driving force These results highlight diverse physicochemical parameters governing behavior suggest how modifications may have evolved robustly tune formation arrest condensates.