Researchers at the University at Buffalo have identified how a microscopic chemical difference between RNA and DNA influences the formation of liquid droplets known as condensates, findings that may help explain how life emerged on early Earth. The research, published in Nature Communications, focuses on a long-standing puzzle in origins-of-life research: RNA would have faced severe obstacles without cellular compartments to contain and protect it. These liquid droplets, which lack membranes but can concentrate RNA molecules in localized areas, may have offered both increased interaction opportunities and protection from harsh environmental conditions.
The study directly compared RNA with single-stranded DNA containing similar molecular sequences. Laboratory experiments revealed that RNA began forming droplets at temperatures approximately 10 degrees Celsius lower than the corresponding DNA, indicating a substantially stronger tendency to condense. Within these droplets, RNA molecules were more likely to form interconnected networks that transitioned from fluid to gel-like structures, changes that could have provided environmental protection during harsh prebiotic conditions.
The research pinpointed the source of this difference to a single oxygen-containing chemical group called the 2′-hydroxyl, present in RNA’s sugar units but absent in DNA. Using temperature-controlled microscopy, X-ray scattering, and computational simulations, the team determined that this 2′-hydroxyl group enables stronger interactions with magnesium ions and affects the water molecules surrounding the RNA backbone, making it easier for RNA molecules to approach one another as temperatures increase. When researchers chemically modified this group to a different form, RNA’s tendency to form condensates decreased significantly.
The findings support RNA world theory, which posits that RNA played a central role in life’s emergence by simultaneously storing genetic information and catalyzing chemical reactions. Current researchers are building on these discoveries by engineering RNA droplets that mimic basic cellular functions, potentially creating synthetic cell-like compartments. This work could eventually demonstrate how simple molecules organized themselves into increasingly complex systems before modern cells developed.
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