ArticleNucleic acids research2022
Kinetic explanations for the sequence biases observed in the nonenzymatic copying of RNA templates.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Nucleoside drives the self-assembly and enables delivery of phosphate containing therapeutics.Materials today. Bio · 2026Article
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- Impact of 2'-deoxyribo-purine substrates on nonenzymatic RNA template-directed primer extension.Nucleic acids research · 2025Article
- Article
- Chirality-Promoted Chemical Ligation and Reverse Transcription ofJournal of the American Chemical Society · 2025Article
- Nonenzymatic RNA copying with a potentially primordial genetic alphabet.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Selection of Early Life Codons by Ultraviolet Light.ACS central science · 2025Article
- Information Gradient among Nucleotide Sequences of Essential RNAs from an Evolutionary Perspective.International journal of molecular sciences · 2024Article
- RNA Complexes with Nicks and Gaps: Thermodynamic and Kinetic Effects of Coaxial Stacking and Dangling Ends.Journal of the American Chemical Society · 2024Article
- Simulations predict preferred MgBiophysical journal · 2024Article
- Diaminopurine in Nonenzymatic RNA Template Copying.Journal of the American Chemical Society · 2024Article
- Constraints on the emergence of RNA through non-templated primer extension with mixtures of potentially prebiotic nucleotides.Nucleic acids research · 2024Article
- Catalytic Metal Ion-Substrate Coordination during Nonenzymatic RNA Primer Extension.Journal of the American Chemical Society · 2024Article
- Transient states during the annealing of mismatched and bulged oligonucleotides.Nucleic acids research · 2024Article
- Natural soda lakes provide compatible conditions for RNA and membrane function that could have enabled the origin of life.PNAS nexus · 2024Article
- Unusual Base Pair between Two 2-Thiouridines and Its Implication for Nonenzymatic RNA Copying.Journal of the American Chemical Society · 2024Article
- Replication elongates short DNA, reduces sequence bias and develops trimer structure.Nucleic acids research · 2024Article
- Thermodynamics and kinetics of DNA and RNA dinucleotide hybridization to gaps and overhangs.Biophysical journal · 2023Article
- Rapid Chemical Ligation of DNA andJournal of the American Chemical Society · 2023Article
- Enhanced nonenzymatic RNA copying with in-situ activation of short oligonucleotides.Nucleic acids research · 2023Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
The identification of nonenzymatic pathways for nucleic acid replication is a key challenge in understanding the origin of life. We have previously shown that nonenzymatic RNA primer extension using 2-aminoimidazole (2AI) activated nucleotides occurs primarily through an imidazolium-bridged dinucleotide intermediate. The reactive nature and preorganized structure of the intermediate increase the efficiency of primer extension but remain insufficient to drive extensive copying of RNA templates containing all four canonical nucleotides. To understand the factors that limit RNA copying, we synthesized all ten 2AI-bridged dinucleotide intermediates and measured the kinetics of primer extension in a model system. The affinities of the ten dinucleotides for the primer/template/helper complexes vary by over 7,000-fold, consistent with nearest neighbor energetic predictions. Surprisingly, the reaction rates at saturating intermediate concentrations still vary by over 15-fold, with the most weakly binding dinucleotides exhibiting a lower maximal reaction rate. Certain noncanonical nucleotides can decrease sequence dependent differences in affinity and primer extension rate, while monomers bridged to short oligonucleotides exhibit enhanced binding and reaction rates. We suggest that more uniform binding and reactivity of imidazolium-bridged intermediates may lead to the ability to copy arbitrary template sequences under prebiotically plausible conditions.
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