A Single Oxygen Atom Lets RNA Form Droplets 10°C Cooler Than DNA, a Clue to How Life Began
University at Buffalo physicists find that the one atom separating RNA from DNA lets it clump into liquid-like droplets that could have sheltered early life's molecules.
RNA and DNA differ by a single oxygen atom, and a new study says that tiny difference may help explain how the first genetic molecules survived on the early Earth. RNA, researchers found, clumps into liquid-like droplets at temperatures roughly 10 degrees Celsius lower than comparable DNA, and it does so far more readily.
The work was led by Priya R. Banerjee, the Twentieth Century Club Professor in the Department of Physics at the University at Buffalo, with Jerelle Joseph of Princeton University's chemical and biological engineering department. It was published July 31 in Nature Communications. The authors are Gable M. Wadsworth, Dilimulati Aierken, George M. Thurston, Joseph and Banerjee, and the work was supported by the National Institutes of Health, the National Science Foundation and the Hypothesis Fund.
The oxygen atom sits in a spot chemists call the 2'-hydroxyl group, or 2'-OH, on RNA's sugar backbone. DNA's sugar lacks it. "This single oxygen-containing group on RNA's sugar has a surprisingly powerful effect" on how the molecules assemble and what the resulting material is like, Banerjee said.
The puzzle the study addresses is a classic one in origin-of-life research. In the RNA world hypothesis, RNA both stored genetic information and performed chemistry, before DNA and proteins took over. But RNA is fragile, and in an open primordial soup its molecules would rarely bump into each other, while hot, acidic conditions would tear them apart. Droplets offer a way around that. They would concentrate RNA and could shield it, without needing a cell membrane.
The team used temperature-controlled microscopy, small-angle X-ray scattering and molecular dynamics simulations to see how the 2'-OH group changes behavior. They found it strengthens RNA's interactions with magnesium ions while reducing the water molecules around each strand, which helps strands stick together. The same chemistry makes RNA droplets more likely to harden into rigid, gel-like networks as temperatures rise.
That has two sides for the origin-of-life story. Easier droplet formation means RNA could have gathered into compartments across a wider range of conditions than DNA. A tendency to gel could also trap molecules, so the balance between liquid and solid may have been part of what made early RNA chemistry workable.
The result also shows how small changes in molecular chemistry can control large self-organized structures, a point relevant to modern cells, which use droplet-like condensates to organize their contents. Many diseases, including some neurodegenerative conditions, involve condensates that turn solid.
Banerjee's lab now plans to engineer RNA droplets that perform basic cell-like functions, with the goal of building synthetic RNA-based compartments from scratch. If they succeed, the droplets would be a test of the idea that life's first containers were not membranes but liquid.
