Enzyme‐Free Copying of 12 Bases of RNA with Dinucleotides
Open accessAbstract
The synthesis of complementary strands is the reaction underlying the replication of genetic information. It is likely that the earliest self‐replicating systems used RNA as genetic material. How RNA was copied in the absence of enzymes and what sequences were most likely to have supported replication is not clear. Here we show that mixtures of dinucleotides with C and G as bases copy an RNA sequence of up to 12 nucleotides in dilute aqueous solution. Successful enzyme‐free copying occurred with in situ activation at 4 °C and pH 6.0. Dimers were incorporated in favor of monomers when both competed as reactants, and little misincorporation was detectable in mass spectra. Simulations using experimental rate constants confirmed that mixed C/G sequences are good candidates for successful replication with dimers. Because dimers are intermediates in the synthesis of longer strands, our results support evolutionary scenarios encompassing formation and copying of RNA strands in enzyme‐free fashion.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Dinucleotides increase affinity to the template.
“dinucleotides to increase affinity to the template.11”
From Sequencing of <scp>d</scp>/<scp>l</scp>-DNA and XNA by Templated-Synthesis (2025) · cites this paper as [11]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Prebiotic Systems Chemistry: New Perspectives for the Origins of Life
Ruiz-Mirazo, K., Briones, C., & de la Escosura, A. (2014) · Chemical Reviews · doi:10.1021/cr2004844 · Cited by 930 · see citing works
Chiral selection in poly(C)-directed synthesis of oligo(G)
Joyce, G. F., Visser, G. M., van Boeckel, C. A. A., van Boom, J. H., Orgel, L. E., & van Westrenen, J. (1984) · Nature · doi:10.1038/310602a0 · Cited by 398 · see citing works
Autocatalytic synthesis of a tetranucleotide analogue
Zielinski, W. S., & Orgel, L. E. (1987) · Nature · doi:10.1038/327346a0 · Cited by 310 · see citing works
Efficient enzyme-free copying of all four nucleobases templated by immobilized RNA
Deck, C., Jauker, M., & Richert, C. (2011) · Nature Chemistry · doi:10.1038/nchem.1086 · Cited by 155 · see citing works
Self-citationThe limits of template-directed synthesis with nucleoside-5′-phosphoro(2-methyl)imidazolides
Hill, A. R., Orgel, L. E., & Wu, T. (1993) · Origins of life and evolution of the biosphere · doi:10.1007/bf01582078 · Cited by 92 · see citing works
Cascade of reduced speed and accuracy after errors in enzyme-free copying of nucleic acid sequences
Leu, K., Kervio, E., Obermayer, B., Turk-MacLeod, R. M., Yuan, C., Luevano, J.-M., Chen, E., Gerland, U., Richert, C., & Chen, I. A. (2013) · Journal of the American Chemical Society · doi:10.1021/ja3095558 · Cited by 78 · see citing works
Self-citationCopying of RNA Sequences without Pre‐Activation
Jauker, M., Griesser, H., & Richert, C. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201506592 · Cited by 72 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 30
- [2]E. V. Koonin, V. V. Dolja, M. Krupovic, A. Varsani, Y. I. Wolf, N. Yutin, F. Murilo Zerbini, J. H. Kuhn, Microbiol. Mol. Biol. Rev. 2020, 84, e00061. 32132243 PMC7062200
- [3]K. Ruiz-Mirazo, C. Briones, A. de la Escosura, Chem. Rev. 2014, 114, 285– 366. 24171674
- [4]I. A. Kozlov, L. E. Orgel, Mol. Biol. 2000, 34, 781– 789. 11153470
- [5]S. A. Benner, H.-J. Kim, Z. Yang, Cold Spring Harbor Perspect. Biol. 2012, 4, a003541. PMC3249627 20880988
- [6]R. M. Turk, N. V. Chumachenko, M. Yarus, Proc. Natl. Acad. Sci. USA 2010, 107, 4585- 4589. 20176971 PMC2826339
- [7]J. Sulston, R. Lohrmann, L. E. Orgel, H. T. Miles, Proc. Natl. Acad. Sci. USA 1968, 59, 726– 733. 5238657 PMC224735
- [8]G. F. Joyce, G. M. Visser, C. A. A. van Boeckel, J. H. van Boom, L. E. Orgel, J. van Westrenen, Nature 1984, 310, 602– 604. 6462250
- [9]A. R. Hill, L. E. Orgel, T. Wu, Origins Life Evol. Biospheres 1993, 23, 285– 290. 8115162
- [10]M. Zielinski, I. A. Kozlov, L. E. Orgel, Helv. Chim. Acta 2000, 83, 1678– 1684. 11543568
- [11]D. Duzdevich, C. E. Carr, D. Ding, S. J. Zhang, T. S. Walton, J. W. Szostak, Nucleic Acids Res. 2021, 49, 3681– 3691. 33744957 PMC8053118
- [12]C. Deck, M. Jauker, C. Richert, Nat. Chem. 2011, 3, 603– 608. 21778979
- [13]L. Li, N. Prywes, C. P. Tam, D. K. O'Flaherty, V. S. Lelyveld, E. C. Izgu, A. Pal, J. W. Szostak, J. Am. Chem. Soc. 2017, 139, 1810– 1813. 28117989 PMC6326525
- [14]N. Prywes, J. C. Blain, F. Del Frate, J. W. Szostak, eLife 2016, 5, e17756. 27351102 PMC4959843
- [15]N. G. Dolinnaya, N. I. Sokolova, D. T. Ashirbekova, Z. A. Shabarova, Nucleic Acids Res. 1991, 19, 3067– 3072. 1711679 PMC328272
- [16]M. Hey, C. Hartel, M. W. Göbel, Helv. Chim. Acta 2003, 86, 844– 854.
- [17]E. Kervio, B. Claasen, U. E. Steiner, C. Richert, Nucleic Acids Res. 2014, 42, 7409– 7420. 24875480 PMC4066754
- [18]M. Jauker, H. Griesser, C. Richert, Angew. Chem. Int. Ed. 2015, 54, 14559– 14563; PMC4678514 26435291 Angew. Chem. 2015, 127, 14767– 14771.
- [19]S. R. Vogel, C. Deck, C. Richert, Chem. Commun. 2005, 4922– 4924. 16205800
- [20]K. Leu, E. Kervio, B. Obermayer, R. M. Turk-MacLeod, C. Yuan, J.-M. Luevano Jr, E. Chen, U. Gerland, C. Richert, I. A. Chen, J. Am. Chem. Soc. 2013, 135, 354– 366. 23259600 PMC3557965
- [21]W. S. Zielinski, L. E. Orgel, Nature 1987, 327, 346– 347. 3587350
- [22]D. Sievers, G. von Kiedrowski, Nature 1994, 369, 221– 224. 8183342
- [23]E. Hänle, C. Richert, Angew. Chem. Int. Ed. 2018, 57, 8911– 8915; 29779237 Angew. Chem. 2018, 130, 9049– 9053.
- [24]M. Sosson, D. Pfeffer, C. Richert, Nucleic Acids Res. 2019, 47, 3836– 3845. 30869145 PMC6486630
- [25]D. Sarracino, C. Richert, Bioorg. Med. Chem. Lett. 1996, 6, 2543– 2548. 11425548
- [26]M. Smietana, E. T. Kool, Angew. Chem. Int. Ed. 2002, 41, 3704– 3707; 12370937 Angew. Chem. 2002, 114, 3856– 3859.
- [27]B. L. Gaffney, E. Veliath, J. Zhao, R. A. Jones, Org. Lett. 2010, 12, 3269– 3271. 20572672 PMC2905038
- [28]E. Edeleva, A. Salditt, J. Stamp, P. Schwintek, J. Boekhoven, D. Braun, Chem. Sci. 2019, 10, 5807– 5814. 31293769 PMC6568275
- [29]C. He, I. Gállego, B. Laughlin, M. A. Grover, N. V. Hud, Nat. Chem. 2017, 9, 318– 324. 28338690
- [30]S. Motsch, P. Tremmel, C. Richert, Nucleic Acids Res. 2020, 48, 1097– 1107. 31819977 PMC7026634
- [31]S. Motsch, D. Pfeffer, C. Richert, ChemBioChem 2020, 21, 2013– 2018. 32017335 PMC7497262
Cited by
Sorted by citations
Prolinyl Nucleotides Drive Enzyme‐Free Genetic Copying of RNA
Welsch, F., Kervio, E., Tremmel, P., & Richert, C. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202307591 · Cited by 13 · see citing works
Self-citationSequencing of <scp>d</scp>/<scp>l</scp>-DNA and XNA by Templated-Synthesis
Joshi, S., Romanens, P., & Winssinger, N. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c00708 · Cited by 4 · see citing works
- Authors
- Leveau, G., Pfeffer, D., Altaner, B., Kervio, E., Welsch, F., Gerland, U., & Richert, C.
- Affiliations
- University of Stuttgart (DE)
- Technical University of Munich (DE)
- Corresponding author
- Richert, Clemens
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2022-05-05
- Volume
- 61
- Issue
- 29
- Pages
- e202203067-e202203067
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- PMC
- PMC9401581
- OpenAlex
- W4226140405
- Cited by
- 23
- References
- 7
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 7 · 2022: 1
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Angewandte Chemie International Edition (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (Project-ID 364653263 - TRR 235 (CRC 235))
- 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
- RNA self-replication, dinucleotides, origin of life, prebiotic chemistry, misincorporation
- MeSH terms
- Nucleotides, RNA, Mass Spectrometry, Dinucleoside Phosphates
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
