Non‐Enzymatic RNA Backbone Proofreading through Energy‐Dissipative Recycling
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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.
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The process can be iterated to replace labile 2',5' linkages with a progressively higher proportion of the more stable 3',5' linkages.
“This process can be iterated to replace labile 2 ′ ,5 ′ linkages, which lead to strand cleavage by transesterification, with a progressively higher proportion of the more stable 3 ′ ,5 ′ linkages”
From Protocells and RNA Self-Replication (2018) · cites this paper as Mariani and Sutherland 2017
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The protometabolic nature of prebiotic chemistry
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The Informational Substrate of Chemical Evolution: Implications for Abiogenesis
de la Escosura, A. (2019) · Life · doi:10.3390/life9030066 · Cited by 9 · see citing works
- Authors
- Mariani, A., & Sutherland, J. D.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Sutherland, John D.
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2017-05-03
- Volume
- 56
- Issue
- 23
- Pages
- 6563-6566
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- PMC
- PMC5488188
- OpenAlex
- W2610545548
- Cited by
- 30
- References
- 5
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 6 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 7 · 2017: 4
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Angewandte Chemie International Edition (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Medical Research Council (MC_UP_A024_1009)
- Simons Foundation (290362)
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- prebiotic chemistry, energy dissipation, acylating agents, RNA duplex formation
- MeSH terms
- Origin of Life, Acetylation, Biopolymers, Chromatography, High Pressure Liquid, Hydrolysis, Phosphates, RNA
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