Evidence map›Paper›PMID 40437192›Full record

ArticleNature chemistry2025

Trinucleotide substrates under pH-freeze-thaw cycles enable open-ended exponential RNA replication by a polymerase ribozyme.

James Attwater, Teresa L Augustin, Joseph F Curran, Samantha L Y Kwok, Luis Ohlendorf, Edoardo Gianni, Philipp Holliger

Abstract read
In one paragraph

Article in Nature chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. The power of triplets.Nature reviews. Chemistry · 2025
    Article
  8. Article
  9. 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

7 authors.

James AttwaterMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK. j.attwater@ucl.ac.uk.ORCID 0000-0002-7244-9910
Teresa L AugustinMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.ORCID 0000-0003-0805-513X
Joseph F CurranMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.ORCID 0000-0002-6660-2747
Samantha L Y KwokMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.ORCID 0009-0009-2632-172X
Luis OhlendorfUCL Department of Chemistry, London, UK.
Edoardo GianniMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.ORCID 0000-0002-5484-2989
Philipp HolligerMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK. ph1@mrc-lmb.cam.ac.uk.ORCID 0000-0002-3440-9854

Funding

RCUK | Medical Research Council (MRC) MC_U105178804Royal Society URF\R1\201271
6 · The paper itself

Abstract

RNA replication is considered a key process in the origins of life. However, both enzymatic and non-enzymatic RNA replication cycles are impeded by the 'strand separation problem', a form of product inhibition arising from the extraordinary stability of RNA duplexes and their rapid reannealing kinetics. Here we show that RNA trinucleotide triphosphates can overcome this problem by binding to and kinetically trapping dissociated RNA strands in a single-stranded form, while simultaneously serving as substrates for replication by an RNA polymerase ribozyme. When combined with coupled pH and freeze-thaw cycles, this enabled exponential replication of both (+) and (-) strands of double-stranded RNAs, including a fragment of the ribozyme itself. Subjecting random RNA sequence pools to open-ended replication yielded either defined replicating RNA sequences or the gradual emergence of diverse sequence pools. The latter derived from partial ribozyme self-replication alongside generation of new RNA sequences, and their composition drifted towards hypothesized primordial codons. These results unlock broader opportunities to model primordial RNA replication.

Indexed as

DNA-Directed RNA PolymerasesRNARNA, CatalyticFreezingHydrogen-Ion ConcentrationKineticsRNA ReplicationSubstrate SpecificityDNA-Directed RNA PolymerasesRNARNA, Catalytic

Identifiers

PMID40437192
PMCPMC12226338

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.