Cited by 264Origins and Evolution of LifeRNA and protein synthesis mechanismsDNA and Biological Computing

A self-replicating ligase ribozyme

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Paul, Natasha, Joyce, Gerald F.·2002·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.202471099

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Authors
Paul, N., & Joyce, G. F.
Affiliations
Scripps Research Institute (US)
Corresponding author
Joyce, Gerald F.
Venue
Proceedings of the National Academy of Sciences
Published
2002-09-18
Volume
99
Issue
20
Pages
12733-12740
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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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