RNA droplets form more readily than DNA, study finds, offering clues to life's origins

Researchers at the University at Buffalo have identified a chemical reason why RNA forms liquid-like droplets more easily than DNA, a finding that supports the idea that such membraneless compartments could have concentrated and protected genetic material before cells existed. The study, published July 31 in Nature Communications, compared RNA with single-stranded DNA of nearly identical sequences.

In temperature-controlled experiments, RNA began forming droplets roughly 10 degrees Celsius lower than the corresponding DNA, indicating a stronger tendency to condense. The RNA droplets also more readily developed interconnected networks, shifting from fluid-like to gel-like states that could better shield molecules from harsh early-Earth conditions.

The key difference lies in a single oxygen atom: each sugar unit in RNA carries a 2′-hydroxyl (2′-OH) group that DNA lacks. Using microscopy, small-angle X-ray scattering, and molecular dynamics simulations, the team found that this group helps RNA interact more strongly with magnesium ions and retain fewer water molecules around its backbone.

Those physical changes promote RNA assembly as temperatures rise. When researchers chemically modified the 2′-OH to a 2′-O-methyl group — a modification found in natural RNA — the molecules' tendency to condense weakened and the resulting condensates stayed more fluid, confirming the group's pivotal role.

Lead corresponding author Priya Banerjee said the work reveals how a tiny chemical change can control the emergence of large, self-organized biomolecular structures. The lab is now engineering RNA droplets to perform basic biochemical reactions, aiming to create active, cell-sized compartments that could model steps toward the first living cells.

The research was conducted in collaboration with Jerelle Joseph's group at Princeton University and funded by the National Institutes of Health, the National Science Foundation, and the Hypothesis Fund.