Kinetic properties of an RNA enzyme that undergoes self-sustained exponential amplification
Open accessAbstract
A special class of biochemical reactions involves a set of enzymes that generate additional copies of themselves and transfer heritable information from parent to progeny molecules, thus providing the basis for genetics and Darwinian evolution. Such a process has been realized with a pair of self-replicating RNA enzymes that undergo exponential amplification at a constant temperature. Exponential growth requires that the rate of production of new enzymes be directly proportional to the existing concentration of enzymes, which is the case for this system and provides a doubling time of ~20 min. However, the catalytic rate of the underlying enzymes is ~100-fold faster than the observed rate of replication. As in biological replication, other aspects of the system limit the generation time, chiefly the propensity of the substrate molecules to form nonproductive complexes that limit their availability for replication. An analysis of this and other kinetic properties of the self-replicating RNA enzymes reveals how exponential amplification is achieved and how the rate of amplification might be increased.
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?
Polymerase ribozymes selected in vitro over decades now have sufficiently high fidelity to accurately copy sequences 80-200 nucleotides long.
“Polymerase ribozymes have been selected in vitro over decades, showing improvement over a series of selections, and now have sufficiently high fidelity to accurately copy sequences 80–200 nucleotides long [94–100].”
From The RNA world as a model system to study the origin of life (2015) · cites this paper as [98]
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
Lee, D. H., Granja, J. R., Martinez, J. A., Severin, K., & Ghadiri, M. R. (1996) · Nature · doi:10.1038/382525a0 · Cited by 677 · see citing works
Self-Sustained Replication of an RNA Enzyme
Lincoln, T. A., & Joyce, G. F. (2009) · Science · doi:10.1126/science.1167856 · Cited by 670 · see citing works
Self-citationA Self‐Replicating Hexadeoxynucleotide
von Kiedrowski, G. (1986) · Angewandte Chemie International Edition in English · doi:10.1002/anie.198609322 · Cited by 583 · see citing works
Mechanism and Utility of an RNA-Cleaving DNA Enzyme
Santoro, S. W., & Joyce, G. F. (1998) · Biochemistry · doi:10.1021/bi9812221 · Cited by 454 · see citing works
Self-citationTjivikua, T., Ballester, P., & Rebek, J. (1990) · Journal of the American Chemical Society · doi:10.1021/ja00159a057 · Cited by 389 · see citing works
Spontaneous network formation among cooperative RNA replicators
Vaidya, N., Manapat, M. L., Chen, I. A., Xulvi-Brunet, R., Hayden, E. J., & Lehman, N. (2012) · Nature · doi:10.1038/nature11549 · Cited by 383 · 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
External Guide Sequences for an RNA Enzyme
Forster, A. C., & Altman, S. (1990) · Science · doi:10.1126/science.1697102 · Cited by 309 · see citing works
A self-replicating ligase ribozyme
Paul, N., & Joyce, G. F. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202471099 · Cited by 264 · see citing works
Self-citationSelf‐Replication by Condensation of 3‐Aminobenzamidines and 2‐Formylphenoxyacetic Acids
Terfort, A., & von Kiedrowski, G. (1992) · Angewandte Chemie International Edition in English · doi:10.1002/anie.199206541 · Cited by 188 · see citing works
Parabolic Growth of a Self‐Replicating Hexadeoxynucleotide Bearing a 3'‐5'‐Phosphoamidate Linkage
von Kiedrowski, G., Wlotzka, B., Helbing, J., Matzen, M., & Jordan, S. (1991) · Angewandte Chemie International Edition in English · doi:10.1002/anie.199104231 · Cited by 171 · see citing works
Self‐Replicating Amphiphilic β‐Sheet Peptides
Rubinov, B., Wagner, N., Rapaport, H., & Ashkenasy, G. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200902790 · Cited by 169 · see citing works
Rapid purification of high-activityTaqDNA polymerase
Pluthero, F. G. (1993) · Nucleic Acids Research · doi:10.1093/nar/21.20.4850 · Cited by 149 · see citing works
T7 RNA polymerase produces 5′ end heterogeneity during in vitro transcription from certain templates
Pleiss, J. A., DERRICK, M. L., & Uhlenbeck, O. C. (1998) · RNA · doi:10.1017/s135583829800106x · Cited by 143 · see citing works
Approaching Exponential Growth with a Self-Replicating Peptide
Issac, R., & Chmielewski, J. (2002) · Journal of the American Chemical Society · doi:10.1021/ja026024i · Cited by 134 · see citing works
Robust self-replication of combinatorial information via crystal growth and scission
Schulman, R., Yurke, B., & Winfree, E. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117813109 · Cited by 132 · see citing works
Self-replication of information-bearing nanoscale patterns
Wang, T., Sha, R., Dreyfus, R., Leunissen, M. E., Maass, C. C., Pine, D. J., Chaikin, P. M., & Seeman, N. C. (2011) · Nature · doi:10.1038/nature10500 · Cited by 123 · see citing works
The effect of cytidine on the structure and function of an RNA ligase ribozyme
Rogers, J., & Joyce, G. F. (2001) · RNA · doi:10.1017/s135583820100228x · Cited by 118 · see citing works
Self-citationA pH-Modulated, Self-Replicating Peptide
Yao, S. Q., Ghosh, I., Zutshi, R., & Chmielewski, J. A. (1997) · Journal of the American Chemical Society · doi:10.1021/ja9710619 · Cited by 117 · see citing works
Cross-catalytic replication of an RNA ligase ribozyme.
Kim, D.-E., & Joyce, G. F. (2004) · Chemistry and Biology · doi:10.1016/j.chembiol.2004.08.021 · Cited by 112 · see citing works
Self-citationMore mistakes by T7 RNA polymerase at the 5′ ends of in vitro-transcribed RNAs
Helm, M., Brulé, H., Giegé, R., & Florentz, C. (1999) · RNA · doi:10.1017/s1355838299982328 · Cited by 82 · see citing works
Autocatalytic aptazymes enable ligand-dependent exponential amplification of RNA
Lam, B. J., & Joyce, G. F. (2009) · Nature Biotechnology · doi:10.1038/nbt.1528 · Cited by 62 · see citing works
Self-citationNelson, J. W., & Tinoco, I. (1982) · Biochemistry · doi:10.1021/bi00264a026 · Cited by 59 · see citing works
Ligand-Dependent Exponential Amplification of a Self-Replicating l -RNA Enzyme
Olea, C., Horning, D. P., & Joyce, G. F. (2012) · Journal of the American Chemical Society · doi:10.1021/ja302197x · Cited by 39 · see citing works
Self-citationSingle-Step Purification of T7 RNA Polymerase with a 6-Histidine Tag
Ellinger, T., & Ehricht, R. (1998) · BioTechniques · doi:10.2144/98245bm03 · Cited by 35 · see citing works
Lam, B. J., & Joyce, G. F. (2011) · Journal of the American Chemical Society · doi:10.1021/ja111136d · Cited by 25 · see citing works
Self-citationSynthetic Evolving Systems that Implement a User-Specified Genetic Code of Arbitrary Design
Sczepanski, J. T., & Joyce, G. F. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.08.017 · Cited by 22 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [13]von Kiedrowski G Dugas H Minimal Replicator Theory I: Parabolic versus Exponential Growth Bioorganic Chemistry 1993 vol. 3 New York Springer-Verlag 115 146
Cited by
Sorted by citations
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
Progress Toward Synthetic Cells
Blain, J. C., & Szostak, J. W. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-080411-124036 · Cited by 314 · see citing works
The RNA world as a model system to study the origin of life
Pressman, A., Blanco, C., & Chen, I. A. (2015) · Current Biology · doi:10.1016/j.cub.2015.06.016 · Cited by 225 · see citing works
Enhanced efficiency of antiseptics with sustained release from clay nanotubes
Wei, W., Minullina, R. T., Abdullayev, E., Fakhrullin, R. F., Mills, D. K., & LVOV, Y. M. (2013) · RSC Advances · doi:10.1039/c3ra45011b · Cited by 140 · see citing works
Iglesias‐Artola, J. M., Drobot, B., Kar, M., Fritsch, A. W., Mutschler, H., Tang, T. ‐. D., & Kreysing, M. (2022) · Nature Chemistry · doi:10.1038/s41557-022-00890-8 · Cited by 125 · see citing works
Highly Efficient Self-Replicating RNA Enzymes
Robertson, M. P., & Joyce, G. F. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2013.12.004 · Cited by 105 · see citing works
Self-citationExploring the emergence of complexity using synthetic replicators
Kosikova, T., & Philp, D. (2017) · Chemical Society Reviews · doi:10.1039/c7cs00123a · Cited by 93 · see citing works
Lipid membranes modulate the activity of RNA through sequence-dependent interactions
Czerniak, T., & Sáenz, J. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2119235119 · Cited by 71 · see citing works
Schneider, C., Becker, S., Okamura, H., Crisp, A. L., Amatov, T., Stadlmeier, M., & Carell, T. (2018) · Angewandte Chemie · doi:10.1002/anie.201801919 · Cited by 54 · see citing works
Thirty-five years of research into ribozymes and nucleic acid catalysis: where do we stand today?
Müller, S., Appel, B., Balke, D., Hieronymus, R., & Nübel, C. (2016) · F1000Research · doi:10.12688/f1000research.8601.1 · Cited by 50 · see citing works
Many Paths to the Origin of Life
Gollihar, J., Levy, M., & Ellington, A. D. (2014) · Science · doi:10.1126/science.1246704 · Cited by 40 · see citing works
Ligand-Dependent Exponential Amplification of a Self-Replicating l -RNA Enzyme
Olea, C., Horning, D. P., & Joyce, G. F. (2012) · Journal of the American Chemical Society · doi:10.1021/ja302197x · Cited by 39 · see citing works
Self-citationClixby, G., & Twyman, L. J. (2016) · Organic & Biomolecular Chemistry · doi:10.1039/c6ob00280c · Cited by 37 · see citing works
When Competing Viruses Unify: Evolution, Conservation, and Plasticity of Genetic Identities
Villarreal, L. P., & Witzany, G. (2015) · Journal of Molecular Evolution · doi:10.1007/s00239-015-9683-y · Cited by 36 · see citing works
Force for ancient and recent life: viral and stem‐loop RNA consortia promote life
Villarreal, L. P. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12565 · Cited by 35 · see citing works
Engineering of hairpin ribozyme variants for RNA recombination and splicing
Hieronymus, R., & Müller, S. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14052 · Cited by 24 · see citing works
Circular RNA (circRNA) was an important bridge in the switch from the RNA world to the DNA world
Soslau, G. (2018) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2018.03.021 · Cited by 23 · see citing works
From prebiotic chemistry to supramolecular oligomers: urea–glyoxal reactions
Lavado, N., de la Concepción, J. G., Gallego, M., Babiano, R., & Cintas, P. (2019) · Organic & Biomolecular Chemistry · doi:10.1039/c9ob01120j · Cited by 17 · see citing works
Real-Time Detection of a Self-Replicating RNA Enzyme
Olea, C., & Joyce, G. F. (2016) · Molecules · doi:10.3390/molecules21101310 · Cited by 12 · see citing works
Self-citationEvolution of RNA-Based Networks
Stadler, P. F. (2015) · Current topics in microbiology and immunology · doi:10.1007/82_2015_470 · Cited by 11 · see citing works
Schneider, C., Becker, S., Okamura, H., Crisp, A., Amatov, T., Stadlmeier, M., & Carell, T. (2018) · Angewandte Chemie · doi:10.1002/ange.201801919 · Cited by 9 · see citing works
New approach to assess sperm DNA fragmentation dynamics: Fine-tuning mathematical models
Ortíz, I., Dorado, J., Morrell, J. M., Gosálvez, J., Crespo, F., Jiménez, J. M. M., & Hidalgo, M. (2017) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-017-0155-7 · Cited by 7 · see citing works
Analysis of supramolecular complex energetics in artificial replicators
Dieckmann, A., & Houk, K. N. (2013) · Chemical Science · doi:10.1039/c3sc51192h · Cited by 7 · see citing works
Encoding Multiple Reactivity Modes within a Single Synthetic Replicator
Robertson, C. C., Kosikova, T., & Philp, D. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c03527 · Cited by 6 · see citing works
Cross-chiral exponential amplification of an RNA enzyme
Cochrane, W. G., Bare, G. A. L., Joyce, G. F., & Horning, D. P. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2413668121 · Cited by 4 · see citing works
Self-citationThe non-canonical nucleotides and prebiotic evolution
Ruzov, A. S., & Ermakov, A. S. (2025) · Biosystems · doi:10.1016/j.biosystems.2025.105411 · Cited by 4 · see citing works
Ligand-Dependent Exponential Amplification of Self-Replicating RNA Enzymes
Olea, C., & Joyce, G. F. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2014.10.030 · Cited by 4 · see citing works
Self-citationSelf‐Replication Without Hydrogen‐Bonds: An Exobiotic Design
Ams, M. R., McAuliffe, J. R., Semenick, R. S., & Zeller, M. (2024) · Chemistry - A European Journal · doi:10.1002/chem.202401446 · Cited by 3 · see citing works
Evolving an Enzyme From a Non-Catalytic Sequence
Gysbers, R. (2015) · MacSphere (McMaster University) · doi:10.71548/15737
Gysbers, R. (2015)
Enabling Darwinian evolution in chemical replicators
Mattia, E. (2017) · University of Groningen research database (University of Groningen / Centre for Information Technology)
Cojocaru, R., & Unrau, P. J. (2021) · Wiley eBooks · doi:10.1002/9783527814527.ch12
From sequence to function: Peptide-nucleotide-based complex coacervates as protocell models
Alanagh, H. R., Younis, M., Wang, J., & Abbas, M. (2026) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2026.103618
- Authors
- Ferretti, A. C., & Joyce, G. F.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Joyce, Gerald F.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-02-05
- Volume
- 52
- Issue
- 7
- Pages
- 1227-1235
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- PMC
- PMC3579227
- OpenAlex
- W2019626555
- Cited by
- 33
- References
- 27
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 5 · 2013: 3 · 2012: 1
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM065130)
- 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 › Genetics › Evolution and Genetic Dynamics
- Keywords
- exponential amplification, RNA self-replication, catalytic kinetics, generation time, autocatalysis
- MeSH terms
- Base Sequence, Kinetics, Models, Chemical, Molecular Sequence Data, Polynucleotide Ligases, RNA, Catalytic, Base Pairing
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