Tiny Chemical Difference in RNA May Explain How Life Began, Study Finds

Before the first cells existed, RNA — a molecule that carries genetic instructions and can also drive chemical reactions — faced a problem: how could it gather in one place and interact with other RNA molecules on a hot, acidic early Earth without any membrane to hold it together? Researchers led by the University at Buffalo, working with Princeton University, say part of the answer lies in RNA's unusual ability to clump into liquid-like droplets called condensates, and they have now pinned down why RNA does this so much more easily than DNA.

Condensates have no membrane, but they can concentrate RNA molecules in a small space, giving them more chances to interact while offering some protection from harsh surroundings. In experiments comparing RNA with single-stranded DNA of nearly the same sequence, the team found that RNA began forming droplets at temperatures about 10 degrees Celsius lower than DNA did, showing a much stronger tendency to condense. RNA also formed interconnected networks inside the droplets more easily, turning the material from a liquid into a more rigid, gel-like structure.

The study, published in Nature Communications, traced this difference to a single chemical group: RNA carries a 2′-hydroxyl (2′-OH) group on each sugar unit that DNA lacks — literally one extra oxygen atom. Using temperature-controlled microscopy, small-angle X-ray scattering and molecular dynamics simulations, the researchers found that the 2′-OH strengthens RNA's interactions with magnesium ions and reduces the number of water molecules around its backbone, both of which make it easier for RNA to gather as temperatures rise.

To confirm the group's role, the researchers chemically converted the 2′-OH into a similar modification called 2′-OMe, found in many natural RNA molecules. The change reduced RNA's tendency to condense and altered whether the resulting droplets stayed fluid or hardened into a gel, the team reported. The research was supported by the National Institutes of Health, the National Science Foundation and the Hypothesis Fund.