Fast and accurate nonenzymatic copying of an RNA-like synthetic genetic polymer
Open accessAbstract
Significance: The first cells to have emerged on the early Earth lacked enzymes, and therefore probably relied on spontaneous reactions to copy their genetic material, commonly thought to have been RNA. Here we study a close chemical relative of RNA, known as 3′-phosphoramidate-DNA, in an effort to learn general lessons about nonenzymatic replication. We show that short regions of this polymer can be copied, but that the error rate is unacceptably high. We then show that a single atom change in one of the four nucleotides can restore good copying accuracy. These advances may help to achieve chemical copying of RNA, and also suggest that 3′-phosphoramidate-DNA may be a suitable genetic polymer for use in the construction of simple artificial cells.
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The G:U wobble pairing problem might be circumvented by a different base pairing system that improves discrimination.
“this might be circumvented by a different base pairing system that improves this discrimination [134].”
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Nonenzymatic primer extension in another system with 3′-amino-2′,3′-dideoxynucleotides exhibits enhanced rates and fidelity upon replacement of T with s2T.
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From Replacing Uridine with 2-Thiouridine Enhances the Rate and Fidelity of Nonenzymatic RNA Primer Extension (2015) · cites this paper as [26]
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- Authors
- Zhang, S., Blain, J. C., Zielinska, D., Gryaznov, S. M., & Szostak, J. W.
- Affiliations
- Howard Hughes Medical Institute (US)
- Geron (United States) (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-10-07
- Volume
- 110
- Issue
- 44
- Pages
- 17732-17737
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3816440
- OpenAlex
- W2152396721
- Cited by
- 80
- References
- 33
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 5 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 8 · 2019: 12 · 2018: 6 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 12
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0809413)
- Howard Hughes Medical Institute
- Division of Chemistry (CHE-0809413)
- 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
- template synthesis, artificial cells, protocells, wobble pairing, polymerization rate
- MeSH terms
- Amides, Chromatography, Liquid, DNA, Genetic Engineering, Phosphoric Acids, Polymers, Mass Spectrometry, Sequence Analysis, DNA, Nucleic Acid Amplification Techniques, Artificial Cells
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