Evidence map›Paper›PMID 30590609›Full record

ArticleNucleic acids research2019

Sensitive ADAR editing reporter in cancer cells enables high-throughput screening of small molecule libraries.

Kajsa Fritzell, Li-Di Xu, Magdalena Otrocka, Claes Andréasson, Marie Öhman

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

28 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
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  7. Regulatable In Vivo Gene Expression via Adaptamers.bioRxiv : the preprint server for biology · 2025
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  12. Review
  13. The role of ADAR1 through and beyond its editing activity in cancer.Cell communication and signaling : CCS · 2024
    Review
  14. Review
  15. Article
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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 1 country.

Kajsa FritzellDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrhenius väg 20C, 106 91 Stockholm, Sweden.
Li-Di XuDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrhenius väg 20C, 106 91 Stockholm, Sweden.
Magdalena OtrockaChemical Biology Consortium Sweden, Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77, Stockholm, Sweden.
Claes AndréassonDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrhenius väg 20C, 106 91 Stockholm, Sweden.
Marie ÖhmanDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrhenius väg 20C, 106 91 Stockholm, Sweden.
Stockholm University · SEScience for Life Laboratory · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adenosine to inosine editing is common in the human transcriptome and changes of this essential activity is associated with disease. Children with ADAR1 mutations develop fatal Aicardi-Goutières syndrome characterized by aberrant interferon expression. In contrast, ADAR1 overexpression is associated with increased malignancy of breast, lung and liver cancer. ADAR1 silencing in breast cancer cells leads to increased apoptosis, suggesting an anti-apoptotic function that promotes cancer progression. Yet, suitable high-throughput editing assays are needed to efficiently screen chemical libraries for modifiers of ADAR1 activity. We describe the development of a bioluminescent reporter system that facilitates rapid and accurate determination of endogenous editing activity. The system is based on the highly sensitive and quantitative Nanoluciferase that is conditionally expressed upon reporter-transcript editing. Stably introduced into cancer cell lines, the system reports on elevated endogenous ADAR1 editing activity induced by interferon as well as knockdown of ADAR1 and ADAR2. In a single-well setup we used the reporter in HeLa cells to screen a small molecule library of 33 000 compounds. This yielded a primary hit rate of 0.9% at 70% inhibition of editing. Thus, we provide a key tool for high-throughput identification of modifiers of A-to-I editing activity in cancer cells.

Indexed as

High-Throughput Screening AssaysAdenosineAdenosine DeaminaseApoptosisAutoimmune Diseases of the Nervous SystemGene EditingGenes, ReporterHeLa CellsHumansInosineInterferonsLuciferasesLuminescent MeasurementsNanoparticlesNeoplasmsNervous System MalformationsADARB1 protein, humanADAR protein, humanAdenosineAdenosine DeaminaseInosineInterferonsLuciferasesRNA-Binding ProteinsSmall Molecule Libraries

Identifiers

PMID30590609
PMCPMC6393238
OpenAlexW2906483477

What OpenQuestion holds

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LicenceCC BY
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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.