Evidence map›Paper›PMID 35446612›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Freeze-thaw cycles enable a prebiotically plausible and continuous pathway from nucleotide activation to nonenzymatic RNA copying.

Stephanie J Zhang, Daniel Duzdevich, Dian Ding, Jack W Szostak

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed.

  1. Article
  2. UV photodamage pathways and the evolutionary selection of thymine over uracil in early genetic systems.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. Article
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  8. Review
  9. Evolution of the substrate specificity of an RNA ligase ribozyme from phosphorimidazole to triphosphate activation.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Article
  11. Article
  12. Simulations predict preferred MgBiophysical journal · 2024
    Article
  13. Diaminopurine in Nonenzymatic RNA Template Copying.Journal of the American Chemical Society · 2024
    Article
  14. Article
  15. High-Fidelity RNA Copying via 2',3'-Cyclic Phosphate Ligation.Journal of the American Chemical Society · 2024
    Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Stephanie J ZhangDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.
Daniel DuzdevichDepartment of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114.ORCID 0000-0002-8225-6071
Dian DingDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.
Jack W SzostakDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.ORCID 0000-0003-4131-1203

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

Nonenzymatic template-directed RNA copying using chemically activated nucleotides is thought to have played a key role in the emergence of genetic information on the early Earth. A longstanding question concerns the number and nature of different environments that might have been necessary to enable all of the steps from nucleotide synthesis to RNA copying. Here we explore three sequential steps from this overall pathway: nucleotide activation, synthesis of imidazolium-bridged dinucleotides, and template-directed RNA copying. We find that all three steps can take place in one reaction mixture undergoing multiple freeze-thaw cycles. Recent experiments have demonstrated a potentially prebiotic methyl isocyanide-based nucleotide activation chemistry. However, the original version of this approach is incompatible with nonenzymatic RNA copying because the high required concentration of the imidazole activating group prevents the accumulation of the essential imidazolium-bridged dinucleotide. Here we report that ice eutectic phase conditions facilitate not only the methyl isocyanide-based activation of ribonucleotide 5′-monophosphates with stoichiometric 2-aminoimidazole, but also the subsequent conversion of these activated mononucleotides into imidazolium-bridged dinucleotides. Furthermore, this one-pot approach is compatible with template-directed RNA copying in the same reaction mixture. Our results suggest that the simple and common environmental fluctuation of freeze-thaw cycles could have played an important role in prebiotic nucleotide activation and nonenzymatic RNA copying.

Indexed as

NucleotidesRNAPolymerizationNucleotidesRNAchemical nucleotide activationorigin of lifeprebiotic chemistryRNA copyingRNA world hypothesis

Identifiers

PMID35446612
PMCPMC9169909

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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.