ISU Chemists Uncover Molecular Driving Forces for RNA-Only Condensate Foundation

Ames, Iowa — Nov. 4, 2025 — In a first-of-its-kind computational study, researchers at Iowa State University have shown how RNA molecules alone can phase-separate into dynamic droplets—without any proteins—to sense and respond to changes in temperature and ions.

Using atomistic simulations, PhD student Vysakh Ramachandran and Associate Professor Davit A. Potoyan uncovered how magnesium ions and RNA sequence chemistry jointly drive this behavior. They found that Mg²⁺ ions act as molecular switches, promoting condensation as temperature rises—a hallmark of lower-critical-solution-temperature (LCST) systems. The simulations reveal that guanine-rich RNAs form the most stable condensates, while RNA’s unique 2′-hydroxyl group and chemical modifications such as m⁶A fine-tune droplet stability.

The work establishes the first molecular-level blueprint for RNA thermo- and iono-sensing, suggesting how living cells could exploit RNA condensates as responsive compartments that reorganize in changing environments.

Published in Proceedings of the National Academy of Sciences (PNAS, DOI: 10.1073/pnas.2511348122), this study opens new directions for understanding and engineering RNA-based phase transitions in biology and nanotechnology.

https://www.pnas.org/doi/10.1073/pnas.2511348122