A new class of ribozyme ligases was found to join RNA only when the substrate carries a 3′-terminal phosphate, revealing an unexpected catalytic reaction from an in vitro evolution experiment.
More than 60% of the selected RNA population showed this activity, catalyzing attack by a substrate’s 2′-hydroxyl on the ribozyme’s 5′-triphosphate to form a noncanonical 2′-5′ linkage.
CS1, the lead ribozyme, captured 3′-phosphorylated RNA from mixed cellular tRNAs even with tRNAs in 60-fold excess, and signal rose linearly across 0.05 to 0.4 µM target concentrations.
The ribozymes ignored standard 3′-OH RNA ends but could capture 2′,3′-cyclic phosphate RNAs after mild acid treatment converted them into 3′-phosphate-containing substrates.
The findings suggest primordial RNA-based cells may have used similar chemistry for RNA repair, while modern labs could adapt the ligases to enrich hard-to-detect RNA cleavage products for transcriptomics.
Beyond finding broken RNA, could these new enzymes be engineered to edit genes inside living cells?
Could RNA have repaired its own genetic code, making the dawn of life more robust than we imagined?
Landmark Discovery of Novel RNA Repair Ribozyme Reveals Mechanism Bridging Origin of Life and Biotechnological Innovation (2026)
Overview
In July 2026, a team led by Assistant Professor Saurja DasGupta made a landmark discovery by unveiling a novel RNA repair ribozyme through experiments using in vitro evolution. This breakthrough sheds new light on the mechanisms of RNA repair and highlights the immense potential of experimental evolution to reveal fundamental biological processes. The discovery not only deepens our understanding of the origins of life but also holds profound implications for the future of biotechnology, as it blurs the line between ancient molecular biology and modern applications. The collaborative effort promises to inspire further exploration into RNA repair and its potential uses.