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Non-Enzymatic RNA Backbone Proofreading through Energy-Dissipative Recycling.

ABSTRACT: Non-enzymatic oligomerization of activated ribonucleotides 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 non-enzymatic 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.

SUBMITTER: Mariani A

PROVIDER: S-EPMC5488188 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Non-Enzymatic RNA Backbone Proofreading through Energy-Dissipative Recycling.

Mariani Angelica A Sutherland John D JD

Angewandte Chemie (International ed. in English) 20170503 23

Non-enzymatic oligomerization of activated ribonucleotides 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 non-enzymatic 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 phosph ...[more]

PMID: 28467695

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