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A self-replicating ligase ribozyme
Open accessAbstract
A self-replicating molecule directs the covalent assembly of component molecules to form a product that is of identical composition to the parent. When the newly formed product also is able to direct the assembly of product molecules, the self-replicating system can be termed autocatalytic. A self-replicating system was developed based on a ribozyme that catalyzes the assembly of additional copies of itself through an RNA-catalyzed RNA ligation reaction. The R3C ligase ribozyme was redesigned so that it would ligate two substrates to generate an exact copy of itself, which then would behave in a similar manner. This self-replicating system depends on the catalytic nature of the RNA for the generation of copies. A linear dependence was observed between the initial rate of formation of new copies and the starting concentration of ribozyme, consistent with exponential growth. The autocatalytic rate constant was 0.011 min −1 , whereas the initial rate of reaction in the absence of pre-existing ribozyme was only 3.3 × 10 −11 M⋅min −1 . Exponential growth was limited, however, because newly formed ribozyme molecules had greater difficulty forming a productive complex with the two substrates. Further optimization of the system may lead to the sustained exponential growth of ribozymes that undergo self-replication.
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“Gerald Joyce (1956–) and coworkers have been able to produce an RNA ligase capable of self-replication in vitro [118].”
From Opinion: The Key Steps in the Origin of Life to the Formation of the Eukaryotic Cell (2024) · cites this paper as [118]
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Metadata
- Authors
- Paul, N., & Joyce, G. F.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Joyce, Gerald F.
- ORCID
- Joyce, Gerald F.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-09-18
- Volume
- 99
- Issue
- 20
- Pages
- 12733-12740
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC130529
- OpenAlex
- W2053143020
- Cited by
- 264
- References
- 0
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 22 · 2023: 8 · 2022: 12 · 2021: 12 · 2020: 13 · 2019: 12 · 2018: 6 · 2017: 10 · 2016: 9 · 2015: 12 · 2014: 11 · 2013: 11 · 2012: 8
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Aeronautics and Space Administration (NAG59386)
- 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
- Physical Sciences › Mathematics › Theoretical Computer Science › DNA and Biological Computing
- Keywords
- RNA ligation, autocatalysis, RNA catalysis, exponential growth, RNA self-assembly
- MeSH terms
- Base Sequence, Biochemical Phenomena, Biochemistry, Catalysis, Dose-Response Relationship, Drug, Escherichia coli, Kinetics, Molecular Sequence Data, Polynucleotide Ligases, RNA Ligase (ATP), Sequence Homology, Nucleic Acid, Time Factors, Transcription, Genetic, RNA, Catalytic, Dimerization
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