Eutectic phase polymerization of activated ribonucleotide mixtures yields quasi-equimolar incorporation of purine and pyrimidine nucleobases
Abstract
The RNA world hypothesis requires a plausible mechanism by which RNA itself (or precursor RNA-like polymers) can be synthesized nonenzymatically from the corresponding building blocks. Simulation experiments have exploited chemically reactive mononucleotides as monomers. Solutions of such monomers in the prebiotic environment were likely to be very dilute, but in experimental simulations of polymerization reactions dilute solutions of activated mononucleotides in the millimolar range hydrolyze extensively, and only trace amounts of dimers and trimers are formed. We report here that random medium-size RNA analogues with mixed sequences (5- to 17-mers with traces of longer products) can be synthesized in ice eutectic phases that are produced when dilute solutions of activated monomers and catalysts (Mg(II) and Pb(II)) are frozen and maintained at -18 degrees C for periods up to 38 days. Under these conditions, the monomers are concentrated as eutectics in an ice matrix. Hydrolysis of the activated mononucleotides was suppressed at low-temperature ranges, and polymerization was enhanced with yields up to 90%. Analysis of the mixed oligomers established that incorporation of both purine and pyrimidine bases proceeded at comparable rates and yields. These results suggest that ice deposits on the early Earth could have facilitated the synthesis of short- and medium-size random sequence RNA analogues and thereby provided a microenvironment suitable for the formation of biopolymers or their precursors.
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Models of non-enzymatic polymerisation of all four activated ribonucleotides yield pools of di-, tri- and tetranucleotide etc. length oligonucleotides, in decreasing abundance, dominating the population alongside longer products.
“Models of non-enzymatic polymerisation of all four activated ribonucleotides – the presumed source of the first RNA sequences – yield pools of di-, tri- and tetranucleotide etc. length oligonucleotides (in decreasing abundance) dominating the population alongside longer products (Monnard et al., 2003).”
From Ribozyme-catalysed RNA synthesis using triplet building blocks (2018) · cites this paper as Monnard et al., 2003
The reactions were surprisingly well behaved, with little to no side products detectable by MALDI MS.
“Despite the high concentrations, which are reminiscent of what is found in eutectic ice phases,11 the reactions were surprisingly well behaved, with little to no side products detectable by MALDI MS.”
From Copying of RNA Sequences without Pre‐Activation (2015) · cites this paper as [11]
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- Authors
- Monnard, P.-A., Kanavarioti, A., & Deamer, D. W.
- Affiliations
- University of California, Santa Cruz (US)
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2003-10-21
- Volume
- 125
- Issue
- 45
- Pages
- 13734-13740
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W1990942508
- Cited by
- 159
- References
- 6
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 4 · 2023: 4 · 2022: 9 · 2021: 11 · 2020: 9 · 2019: 10 · 2018: 7 · 2017: 10 · 2016: 5 · 2015: 14 · 2014: 6 · 2013: 3 · 2012: 12
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- 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 Nucleic Acid Chemistry
- Keywords
- RNA world, RNA analogues, prebiotic chemistry
- MeSH terms
- Ribonuclease T1, Purines, Pyrimidines, Ribonuclease, Pancreatic, Ribonucleotides, RNA
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