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Peer-reviewedCC BY-NC-NDNature Communications

The role of the 2’-OH group in phase separation and percolation transitions of RNA

  • Gable M. Wadsworth1
  • Dilimulati Aierken2,3
  • George M. Thurston4
  • Jerelle A. Joseph5,6
  • Priya R. Banerjee7
7 affiliations
  1. 1Department of Physics, The State University of New York at Buffalo, Buffalo, NY, USA
  2. 2Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA
  3. 3Omenn-Darling Biological Engineering Institute, Princeton University, Princeton, NJ, USA
  4. 4School of Physics and Astronomy, Rochester Institute of Technology, Rochester, New York, NY, USA
  5. 5Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, USA. [email protected]
  6. 6Omenn-Darling Biological Engineering Institute, Princeton University, Princeton, NJ, USA. [email protected]
  7. 7Department of Physics, The State University of New York at Buffalo, Buffalo, NY, USA. [email protected]
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Abstract

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

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Cite

BibTeXRIS
BibTeX
@article{wadsworth2026role,
  title = {{The role of the 2’-OH group in phase separation and percolation transitions of RNA}},
  author = {Gable M. Wadsworth and Dilimulati Aierken and George M. Thurston and Jerelle A. Joseph and Priya R. Banerjee},
  journal = {Nature Communications},
  year = {2026},
  month = jul,
  doi = {10.1038/s41467-026-75961-2},
  url = {https://doi.org/10.1038/s41467-026-75961-2},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - The role of the 2’-OH group in phase separation and percolation transitions of RNA
AU  - Gable M. Wadsworth
AU  - Dilimulati Aierken
AU  - George M. Thurston
AU  - Jerelle A. Joseph
AU  - Priya R. Banerjee
PY  - 2026
DA  - 2026/07/31
JO  - Nature Communications
DO  - 10.1038/s41467-026-75961-2
UR  - https://doi.org/10.1038/s41467-026-75961-2
AB  - Magnesium ion-dependent RNA liquid-liquid phase separation with lower critical solution temperatures is driven by the phosphate backbone and modulated by the solvation property of nucleobases. Here, we report a key role of the 2’-OH group of the ribose sugar in RNA condensation in the presence of divalent cations. We show that 2’-deoxyribose inhibits nucleic acid phase separation and suppresses the intra-condensate networking transition, known as percolation, that underlies condensate dynamical arrest. All-atom simulations reveal increased solvation and compaction of single-stranded DNA compared to RNA, suggesting an unintuitive role of chain flexibility in modulating heat-induced nucleic acid phase separation and percolation transitions. Further, 2'-O-methylation (2'-O-Me) of RNA, a common sugar modification, lowers the driving force of RNA phase transitions. These results highlight the diverse physicochemical parameters governing nucleic acid phase behavior and suggest how sugar modifications may have evolved to robustly tune the formation and dynamical arrest of RNA condensates.
SN  - 2041-1723
ER  -