Evidence map›Paper›PMID 34020718›Full record

ArticleActa neuropathologica communications2021

In vivo 5-ethynyluridine (EU) labelling detects reduced transcription in Purkinje cell degeneration mouse mutants, but can itself induce neurodegeneration.

Lisanne J Van't Sant, Joshua J White, Jan H J Hoeijmakers, Wilbert P Vermeij, Dick Jaarsma

Open access · goldAbstract read
In one paragraph

Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

11 citing papers in PubMed, 20 citations in OpenAlex.

  1. Bioorthogonal Chemistry in Neurobiology: From Imaging to Proteomics.Chembiochem : a European journal of chemical biology · 2026
    Review
  2. Article
  3. Review
  4. Article
  5. RNA Decay Assay: 5-Ethynyl-Uridine Labeling and Chasing.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  6. Article
  7. Click Chemistry for Visualization of Newly Synthesized RNA and Antibody Labeling on Ultrathin Tissue Sections.Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada · 2023
    Article
  8. Article
  9. Cycloaddition enabled mutational profiling of 5-vinyluridine in RNA.Chemical communications (Cambridge, England) · 2023
    Article
  10. Article
  11. 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

5 authors at 2 institutions in 2 countries.

Lisanne J Van't SantDepartment of Neuroscience, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Joshua J WhiteDepartment of Neuroscience, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Jan H J HoeijmakersDepartment of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
Wilbert P VermeijPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Dick JaarsmaDepartment of Neuroscience, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. d.jaarsma@erasmusmc.nl.ORCID 0000-0002-0519-2940
Erasmus MC · NLOncode Institute · NL

Funding

THE IMPACT OF CELLULAR DEFENSE ON THE ROLE OF Ku80 IN GENOME MAINTENANCE AND LONGP01AG017242 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI VIJG, JAN · 1999 to 2023
$46.1M
NIA NIH HHS P01 AG017242
6 · The paper itself

Abstract

Fluorescent staining of newly transcribed RNA via metabolic labelling with 5-ethynyluridine (EU) and click chemistry enables visualisation of changes in transcription, such as in conditions of cellular stress. Here, we tested whether EU labelling can be used to examine transcription in vivo in mouse models of nervous system disorders. We show that injection of EU directly into the cerebellum results in reproducible labelling of newly transcribed RNA in cerebellar neurons and glia, with cell type-specific differences in relative labelling intensities, such as Purkinje cells exhibiting the highest levels. We also observed EU-labelling accumulating into cytoplasmic inclusions, indicating that EU, like other modified uridines, may introduce non-physiological properties in labelled RNAs. Additionally, we found that EU induces Purkinje cell degeneration nine days after EU injection, suggesting that EU incorporation not only results in abnormal RNA transcripts, but also eventually becomes neurotoxic in highly transcriptionally-active neurons. However, short post-injection intervals of EU labelling in both a Purkinje cell-specific DNA repair-deficient mouse model and a mouse model of spinocerebellar ataxia 1 revealed reduced transcription in Purkinje cells compared to controls. We combined EU labelling with immunohistology to correlate altered EU staining with pathological markers, such as genotoxic signalling factors. These data indicate that the EU-labelling method provided here can be used to identify changes in transcription in vivo in nervous system disease models.

Indexed as

AnimalsFemaleMaleMiceMice, Inbred C57BLMice, TransgenicMutationNerve DegenerationNeurodegenerative DiseasesPurkinje CellsStaining and LabelingTranscription, GeneticUridineUridine5-EthynylurdineDNA damageErcc1Nascent RNAPurkinje cell degenerationSCA1Transcription stress

Identifiers

PMID34020718
PMCPMC8139001
OpenAlexW3163528200

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.