3′-Phosphate–Dependent Ribozyme Ligases Hint at RNA-Repair Pathways in Early Life
Researchers discovered four classes of ribozyme ligases that catalyze a novel ligation: the substrate’s 2′-OH attacks the ribozyme’s own 5′-triphosphate only when the substrate bears a neighboring 3′-phosphate, producing a 2′–5′ phosphodiester bond. These ligases show strict dependence on a 3′-phosphate and can ligate even without an external template (for at least one variant), with Mg2+ likely helping localize catalytic ions. In addition to revealing a new RNA-catalysis mode, the authors demonstrate selective capture and amplification of 3′-phosphorylated RNAs from mixed cellular RNA, offering a potential transcriptomics reagent to profile RNA cleavage products. The work also provides a plausible, salvage-like RNA repair mechanism in the RNA World and highlights how a single selection pressure can yield multiple related ribozymes with shared structural features.