Scientists Discover How RNA Organized Itself Before Cells Existed

A microscopic chemical distinction between ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) may hold the key to understanding how early biological molecules organized themselves before the emergence of cellular membranes. Researchers have determined that an extra oxygen atom, repeated along the RNA backbone, significantly enhances the molecule’s ability to gather into dense, liquid-like droplets compared to similar strands of DNA.

The Membrane-Free Concentration Problem

Modern biology relies on cell membranes to contain useful molecules, isolate internal chemistry from the external environment, and facilitate efficient reactions. Origins-of-life researchers face a significant challenge when modeling biology prior to the existence of cells: without a membrane, how did fragile RNA molecules concentrate sufficiently to interact repeatedly? The RNA world hypothesis suggests RNA served as both genetic carrier and catalyst before DNA and proteins assumed these roles, but individual RNA strands floating in vast bodies of water would struggle to encounter necessary partners due to their lower chemical stability compared to DNA.

Phase Separation as a Solution

One proposed mechanism is phase separation, a process where biomolecules form dense droplets within a dilute solution, analogous to oil separating from water. These structures, known as biomolecular condensates, do not require enclosing membranes. While modern cells utilize condensates extensively, scientists hypothesize that simpler versions could have organized prebiotic chemistry on early Earth. In 2023, a team led by University at Buffalo physicist Priya Banerjee demonstrated that various RNA types spontaneously formed droplets when heated in magnesium-containing solutions, defying the typical expectation that heat promotes dissolution.

How Does the 2′-OH Group Drive Condensation?

The new study investigated why RNA excels at this behavior by comparing it with single-stranded DNA of nearly identical sequence. Both molecules feature genetic letters attached to a sugar-phosphate backbone, but they differ at one specific position: RNA contains ribose with a hydroxyl group (2′-OH) on the second carbon, whereas DNA contains deoxyribose with only a hydrogen atom at that spot. Under experimental conditions, RNA strands began forming condensates at temperatures approximately 10 degrees Celsius lower than their DNA counterparts, indicating a substantially higher tendency for phase separation.

Molecular Interactions and Gel Networks

Using microscopy, X-ray measurements, and molecular simulations, the researchers found that the 2′-OH group alters how RNA interacts with water and magnesium ions. As temperatures increased, RNA shed its surrounding water molecules more readily than DNA, allowing magnesium ions to pull RNA strands together into dense droplets. These droplets could further develop into interconnected, gel-like networks, a behavior DNA exhibited much less frequently. "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," Banerjee stated in a University at Buffalo release.

First author Gable Wadsworth noted that this single oxygen-containing group exerts a powerful influence on whether molecules aggregate, remain dynamic, or solidify into gel-like materials. This mechanism offers a plausible, though still speculative, pathway for concentrating useful molecules before cells existed, potentially bridging the gap between simple prebiotic chemicals and complex biological organization.