42: Amino acids catalyse RNA formation under ambient alkaline conditions

Rout SK et al., Nature Communications - A Nature Communications study shows that proteinogenic amino acids accelerate non-enzymatic RNA oligomerisation from ribonucleoside-2',3'-cyclic phosphates under dry alkaline conditions at ambient temperature, increasing yields, sequence diversity and the fraction of natural 3'-5' linkages. Key terms: RNA polymerisation, amino acids, prebiotic chemistry, 2',3'-cyclic phosphates, acid-base catalysis.

Study Highlights:
Amino acids catalyse RNA copolymerisation from ribonucleoside-2',3'-cyclic phosphates under dry alkaline conditions, increasing yields by more than 100-fold for some nucleotides. Catalysis peaks near pH 9–10, close to the amine pKa, consistent with an acid–base mechanism in which amine/ammonium pairs facilitate proton transfer during transphosphorylation. Hydrophobic amino acids (Val, Leu, Ile) produced the largest enhancements, reduced the intrinsic G-bias, and increased the fraction of natural 3'-5' linkages and activated 2',3'-cyclic phosphate termini. Molecular dynamics and quantum calculations support preferential amino-acid localisation near phosphate groups to enable the catalytic effect.

Conclusion:
Amino acids can plausibly have played a direct catalytic role in early Earth chemistry by promoting the formation of diverse, replication-capable RNA pools under mild alkaline drying conditions, linking peptides and RNA earlier in chemical evolution than previously assumed.

Music:
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Article title:
Amino acids catalyse RNA formation under ambient alkaline conditions

First author:
Rout SK

Journal:
Nature Communications

DOI:
10.1038/s41467-025-60359-3

Reference:
Rout SK, Wunnava S, Krepl M, Cassone G, Šponer JE, Mast CB, Powner MW & Braun D. Amino acids catalyse RNA formation under ambient alkaline conditions. Nature Communications (2025). doi:10.1038/s41467-025-60359-3

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-06-11.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the core scientific content: dry-state RNA oligomerisation catalysed by amino acids, acid-base mechanism, pH dependence, base distribution, linkage fidelity, and the broader implications for early biogenesis.
- transcript topics: Dry-state RNA oligomerisation with amino acids; Acid-base catalysis and pH dependence around amino acid pKa; Hydrophobic amino acids localising near phosphate center; Nucleobase composition shifts (G/C/A/U) and reduced G-bias; Formation and retention of 3'-5' canonical linkages; Recycling of hydrolysis products to active 2',3'-cyclic phosphates

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 8
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Amino acids catalyse RNA oligomerisation under dry-state alkaline conditions, yielding >100-fold increases.
- Catalysis shows an optimum near pH 9–10, consistent with amino acid pKaH.
- Hydrophobic amino acids (Val, Leu, Ile) provide strongest enhancement and reduce G-bias.
- Amino acid presence increases fraction of canonical 3'-5' linkages to about 58–66%.
- Oligomers retain activated 2',3'-cyclic phosphate termini favorable for templated ligation.
- Mg2+ is not required for the observed polymerisation; the system relies on dry-state acid-base catalysis.

QC result: Pass.