ArticleNucleic acids research2021
Competition between bridged dinucleotides and activated mononucleotides determines the error frequency of nonenzymatic RNA primer extension.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Influence of Phosphate Activation Chemistry on the Selection of the Primordial Genetic Alphabet.Journal of the American Chemical Society · 2026Article
- Impact of 2'-deoxyribo-purine substrates on nonenzymatic RNA template-directed primer extension.Nucleic acids research · 2025Article
- Article
- A quantitative model of enzyme-free copying of RNA with dimers.Nucleic acids research · 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-diversification interplay in oligonucleotide chemical evolution.Biophysics and physicobiology · 2025Article
- Overcoming nucleotide bias in the nonenzymatic copying of RNA templates.Nucleic acids research · 2024Article
- Simulations predict preferred MgBiophysical journal · 2024Article
- Diaminopurine in Nonenzymatic RNA Template Copying.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
- Cyclophospholipids Enable a Protocellular Life Cycle.ACS nano · 2023Article
- Insight into the structures of unusual base pairs in RNA complexes containing a primer/template/adenosine ligand.RSC chemical biology · 2023Article
- Thermodynamics and kinetics of DNA and RNA dinucleotide hybridization to gaps and overhangs.Biophysical journal · 2023Article
- Small-Molecule Organocatalysis Facilitates In Situ Nucleotide Activation and RNA Copying.Journal of the American Chemical Society · 2023Article
- Enhanced nonenzymatic RNA copying with in-situ activation of short oligonucleotides.Nucleic acids research · 2023Article
- Direct monitoring of the thermodynamics and kinetics of DNA and RNA dinucleotide dehybridization from gaps and overhangs.bioRxiv : the preprint server for biology · 2023Article
- Experimental Tests of the Virtual Circular Genome Model for Nonenzymatic RNA Replication.Journal of the American Chemical Society · 2023Article
- Enzyme-Free Copying of 12 Bases of RNA with Dinucleotides.Angewandte Chemie (International ed. in English) · 2022Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Nonenzymatic copying of RNA templates with activated nucleotides is a useful model for studying the emergence of heredity at the origin of life. Previous experiments with defined-sequence templates have pointed to the poor fidelity of primer extension as a major problem. Here we examine the origin of mismatches during primer extension on random templates in the simultaneous presence of all four 2-aminoimidazole-activated nucleotides. Using a deep sequencing approach that reports on millions of individual template-product pairs, we are able to examine correct and incorrect polymerization as a function of sequence context. We have previously shown that the predominant pathway for primer extension involves reaction with imidazolium-bridged dinucleotides, which form spontaneously by the reaction of two mononucleotides with each other. We now show that the sequences of correctly paired products reveal patterns that are expected from the bridged dinucleotide mechanism, whereas those associated with mismatches are consistent with direct reaction of the primer with activated mononucleotides. Increasing the ratio of bridged dinucleotides to activated mononucleotides, either by using purified components or by using isocyanide-based activation chemistry, reduces the error frequency. Our results point to testable strategies for the accurate nonenzymatic copying of arbitrary RNA sequences.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.