Results: RNA condenses at about 10°C lower than DNA. RNA also forms more interconnected networks inside the droplets. As those networks develop, the droplets shift from a fluid state into a more rigid, gel-like material — a structure that could give RNA extra protection against damaging conditions.

Two molecular effects appear to drive the difference. The 2′-OH group lets RNA bind more strongly with magnesium ions. RNA also holds fewer water molecules around its backbone than DNA does. Both effects help RNA strands approach each other more easily as temperatures rise.

To test the idea, the researchers chemically swapped the 2′-OH for a closely related 2′-Ome group, the kind found in many natural RNAs. That single modification weakened RNA's tendency to form condensates. It also altered whether the resulting droplets stayed fluid or gelled.

"This single oxygen-containing group on RNA's sugar has a surprisingly powerful effect on whether these molecules come together, remain dynamic, or become arrested into a gel-like material," said first author Gable Wadsworth, PhD, a postdoc in Banerjee's lab who will join the University of Texas at El Paso as an assistant professor this fall.

Why does this matter for life's origins?

If RNA droplets could harden into protective, gel-like compartments on the early Earth, they might have acted as proto-cells before true membranes appeared.

"These findings reveal, for the first time, how remarkably small changes in molecular chemistry can control the emergence of much larger, self-organized biomolecular structures like RNA condensates," said lead corresponding author Priya R. Banerjee, PhD, the Twentieth Century Club Professor of Physics at UB. "They could allow us to eventually address even deeper questions, like whether these condensates helped bridge the gap between simple molecules and the earliest forms of life."

"These kinds of self-organizing RNA compartments were possibly a step along the way to single-cell organisms," Banerjee added.

What's next?

Banerjee's lab aims to engineer RNA droplets that can perform basic cellular tasks, including running biochemical reactions. If successful, the work could lay the groundwork for synthetic cells built entirely from RNA.

The study extends a 2023 paper from the same group, which first showed that RNA has a strong tendency to form condensates at elevated temperatures. The National Institutes of Health, the National Science Foundation, and the Hypothesis Fund funded the research.

Caveats remain. The experiments used purified molecules under tightly controlled lab conditions. Whether similar condensates form and stabilize in real prebiotic environments — with messy chemistry, temperature swings, and mineral surfaces — is untested. The team also notes that gel-like transitions sometimes trap molecules in unproductive states rather than protect them, an outcome still to be explored.