Scripps Research Study Reveals Ribose's Key Role in RNA Evolution

In a groundbreaking study published on June 27, 2025, in the journal *Angewandte Chemie*, researchers from Scripps Research Institute have elucidated the fundamental role of ribose in the formation of RNA, suggesting it may have been the sugar of choice for early molecular development. This research addresses age-old questions regarding the origins of life's building blocks, particularly how certain sugars, like ribose, became integral to RNA and DNA structures.

The study, led by Professor Ramanarayanan Krishnamurthy and co-authored by Harold A. Cruz, investigated the phosphorylation process, where ribose binds with phosphate—a crucial step in nucleotide formation. "Phosphorylation is one of the basic chemistries of life; it’s essential for structure, function, and metabolism," Krishnamurthy stated, emphasizing the study's significance in understanding prebiotic chemistry.

Previous research indicated that ribose could be phosphorylated by a phosphate-donating molecule known as diamidophosphate (DAP). This recent study aimed to determine whether ribose had unique properties that made it more effective in this role compared to structurally similar sugars: arabinose, lyxose, and xylose. Through controlled chemical reactions and analysis via nuclear magnetic resonance (NMR) spectroscopy, the team found that ribose was phosphorylated significantly faster than its counterparts, producing a predominantly five-member ring structure. This shape is crucial as it aligns with the structural requirements of RNA and DNA.

Krishnamurthy explained, "We showed that ribose is selectively phosphorylated from a mixture of sugars, and we also demonstrated that this selective process produces a molecule conducive for making RNA." This finding supports the hypothesis that ribose's unique reactivity could have contributed to its selection as a primary sugar in the development of life.

However, the researchers caution against claiming that these reactions directly resulted in the emergence of RNA and DNA. "Studying these types of chemistries helps us understand potential processes that led to the molecules constituting life today, but we are not asserting that this selection is what ultimately led to RNA and DNA, as that remains a significant leap," Krishnamurthy clarified.

The implications of this study extend beyond mere biochemical curiosity; they touch upon the origins of life itself. As Krishnamurthy and his team prepare to investigate whether ribose can be selectively enriched within primitive cellular structures called protocells, they may be on the path to uncovering how the first life forms could have emerged from non-living chemical processes. "If we can achieve that, it could lead to understanding how protocells grow and divide—foundational processes for life as we know it," he concluded.

The research, supported by the NASA Astrobiology Exobiology grant (80NSSC22K0509) and published in the journal *Angewandte Chemie*, offers a compelling glimpse into the prebiotic world, suggesting that ribose’s distinctive chemical properties may have played a pivotal role in the development of RNA, and by extension, life itself. This revelation not only enriches our understanding of molecular biology but also paves the way for future inquiries into the origins of life on Earth and beyond.