Non-Enzymatic RNA Backbone Proofreading through Energy-Dissipative Recycling

摘要

Non-enzymatic oligomerization of activated ribo-nucleotides leads to ribonucleic acids that contain a mixture of 2', 5'-and 3', 5'-linkages, and overcoming this backbone heterogeneity has long been considered a major limitation to the prebiotic emergence of RNA. Herein, we demonstrate nonenzymatic chemistry that progressively converts 2', 5'-linkages into 3', 5'-linkages through iterative degradation and repair. The energetic costs of this proofreading are met by the hydrolytic turnover of a phosphate activating agent and an acylating agent. With multiple rounds of this energy-dissipative recycling, we show that all-3', 5'-linked duplex RNA can emerge from a backbone heterogeneous mixture, thereby delineating a route that could have driven RNA evolution on the early earth.