Evidence map›Paper›PMID 31199786›Full record

ArticlePLoS biology2019

Cytosine-5 RNA methylation links protein synthesis to cell metabolism.

Nikoletta A Gkatza, Cecilia Castro, Robert F Harvey, Matthias Heiß, Martyna C Popis, Sandra Blanco, Susanne Bornelöv, Abdulrahim A Sajini, Joseph G Gleeson, Julian L Griffin and 5 more

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
5.9field-weighted citation impact, top 3% of its field
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

92 citing papers in PubMed, 132 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. NSUN2-Mediated mInternational journal of general medicine · 2026
    Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Emerging roles of transfer RNA fragments in the CNS.Brain : a journal of neurology · 2025
    Review
  18. Article
  19. Ribosome-associated proteins: unwRAPping ribosome heterogeneity in the twenty-first century.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Review
  20. Detection, molecular function and mechanisms of m5C in cancer.Clinical and translational medicine · 2025
    Review

32 more citing papers are in PubMed but not listed here.

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

15 authors at 7 institutions in 5 countries.

Nikoletta A GkatzaDepartment of Genetics, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0001-6360-7940
Cecilia CastroDepartment of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
Robert F HarveyMedical Research Council Toxicology Unit, University of Cambridge, Cambridge, United Kingdom.
Matthias HeißDepartment of Chemistry, Ludwig-Maximilians-University Munich, Munich, Germany.ORCID 0000-0002-6770-9511
Martyna C PopisDepartment of Genetics, University of Cambridge, Cambridge, United Kingdom.
Sandra BlancoCancer Cell Signaling and Metabolism Lab, Proteomics Unit CIC bioGUNE, Derio, Spain.ORCID 0000-0001-7352-9392
Susanne BornelövWellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0001-9276-9981
Abdulrahim A SajiniDepartment of Biomedical Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.ORCID 0000-0002-8600-3899
Joseph G GleesonDepartment of Neurosciences, San Diego School of Medicine, University of California, La Jolla, California, United States of America.
Julian L GriffinDepartment of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
James A WestDepartment of Biochemistry, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-1535-7737
Stefanie KellnerDepartment of Chemistry, Ludwig-Maximilians-University Munich, Munich, Germany.ORCID 0000-0003-3224-7502
Anne E WillisMedical Research Council Toxicology Unit, University of Cambridge, Cambridge, United Kingdom.
Sabine DietmannWellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
Michaela FryeDepartment of Genetics, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-5636-6840
University of Cambridge · GBLudwig-Maximilians-Universität München · DEWellcome/MRC Cambridge Stem Cell Institute · GBConsejo Superior de Investigaciones Científicas · ESGerman Cancer Research Center · DEKhalifa University of Science and Technology · AEUniversity of California San Diego · US

Funding

Cancer Research UK 15181Cancer Research UK C10701/A15181Cancer Research UK C10701/A16134Medical Research Council MC_PC_12009Medical Research Council MC_PC_13030Medical Research Council MC_UP_A090_1006Medical Research Council MC_UP_A600_1023Medical Research Council MC_UU_00025/7Medical Research Council MR/M01939X/1Medical Research Council MR/P011705/1Medical Research Council MR/P01836X/1Wellcome Trust
6 · The paper itself

Abstract

Posttranscriptional modifications in transfer RNA (tRNA) are often critical for normal development because they adapt protein synthesis rates to a dynamically changing microenvironment. However, the precise cellular mechanisms linking the extrinsic stimulus to the intrinsic RNA modification pathways remain largely unclear. Here, we identified the cytosine-5 RNA methyltransferase NSUN2 as a sensor for external stress stimuli. Exposure to oxidative stress efficiently repressed NSUN2, causing a reduction of methylation at specific tRNA sites. Using metabolic profiling, we showed that loss of tRNA methylation captured cells in a distinct catabolic state. Mechanistically, loss of NSUN2 altered the biogenesis of tRNA-derived noncoding fragments (tRFs) in response to stress, leading to impaired regulation of protein synthesis. The intracellular accumulation of a specific subset of tRFs correlated with the dynamic repression of global protein synthesis. Finally, NSUN2-driven RNA methylation was functionally required to adapt cell cycle progression to the early stress response. In summary, we revealed that changes in tRNA methylation profiles were sufficient to specify cellular metabolic states and efficiently adapt protein synthesis rates to cell stress.

Indexed as

AnimalsCell LineCytosineDNA-Cytosine MethylasesDNA MethylationHumansMethyltransferasesMiceOxidative StressProtein BiosynthesisRNARNA, TransferCytosineCytosine 5-methyltransferaseDNA-Cytosine MethylasesMethyltransferasesNSUN2 protein, humanRNARNA, Transfer

Identifiers

PMID31199786
PMCPMC6594628
OpenAlexW2952226193

What OpenQuestion holds

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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.