Evidence map›Paper›PMID 36864190›Full record

ArticleNature chemical biology2023

Remodeling oncogenic transcriptomes by small molecules targeting NONO.

Stefan G Kathman, Seong Joo Koo, Garrett L Lindsey, Hsuan-Lin Her, Steven M Blue, Haoxin Li, Steffen Jaensch, Jarrett R Remsberg, Kay Ahn, Gene W Yeo and 2 more

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
12.6field-weighted citation impact, top 1% 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

61 citing papers in PubMed, 82 citations in OpenAlex.

  1. Article
  2. Article
  3. Engineering a protein homodimer from a heterodimer: A chimeric DBHS protein.Protein science : a publication of the Protein Society · 2026
    Article
  4. The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Targeting extrachromosomal DNA in human cancers.Nature reviews. Drug discovery · 2026
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

1 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

12 authors at 4 institutions in 2 countries.

Stefan G Kathman *Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA. skathman@scripps.edu.ORCID http://orcid.org/0000-0002-4755-9907
Seong Joo Koo *Molecular and Cellular Pharmacology, Discovery Technologies and Molecular Pharmacology, Janssen Research and Development, Beerse, Belgium.
Garrett L Lindsey *Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
Hsuan-Lin HerBioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, USA.
Steven M BlueDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Haoxin LiDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
Steffen JaenschHigh Dimensional and Computational Biology, Discovery Technologies and Molecular Pharmacology, Janssen Research and Development, Beerse, Belgium.
Jarrett R RemsbergDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-5234-0168
Kay AhnMolecular and Cellular Pharmacology, Discovery Technologies and Molecular Pharmacology, Janssen Research and Development, Spring House, PA, USA. kayahn2@gmail.com.ORCID http://orcid.org/0000-0001-9139-1534
Gene W YeoDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. geneyeo@ucsd.edu.ORCID http://orcid.org/0000-0002-0799-6037
Brahma GhoshDiscovery Chemistry, Janssen Research and Development, Spring House, PA, USA. bghosh7@its.jnj.com.ORCID http://orcid.org/0000-0003-2288-8293
Benjamin F CravattDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA, USA. cravatt@scripps.edu.ORCID http://orcid.org/0000-0001-5330-3492
Scripps Research Institute · USUniversity of California San Diego · USJanssen (Belgium) · BESpringhouse · US

Funding

Functional RNA elements in the human genomeR01HG004659 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kevin Daniel Corbett, Eugene Wei-Ming Yeo · 2008 to 2026
$12.4M
Chemical Proteomic Platforms for Radically Expanding Cancer DruggabilityR35CA231991 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI BENJAMIN F CRAVATT · 2018 to 2026
$9.5M
A Comprehensive Functional Map of Human Protein-RNA InteractionsU41HG009889 · NHGRI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI GRAVELEY, BRENTON R. · 2018 to 2021
$9.4M
Integrated ligand and target discovery by chemical proteomics for glioblastoma treatment.R01CA238249 · NCI · STANFORD UNIVERSITY · PI CRAVATT, BENJAMIN F, MISCHEL, PAUL S · 2021 to 2025
$3.3M
Analysis of functional genetic variants in RNA processing and expressionU01HG009417 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI XIAO, XINSHU GRACE · 2017 to 2021
$3.2M
Analysis of RNA binding proteins directing hematopoietic stem cell fateR01HL137223 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HOPE, KRISTIN, YEO, EUGENE WEI-MING · 2018 to 2021
$2.5M
Characterization and modulation of ferroptosis by chemical proteomicsF32CA228436 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI KATHMAN, STEFAN GRUBOW · 2018 to 2020
$187k
NCI NIH HHS F32 CA228436NCI NIH HHS R01 CA238249NCI NIH HHS R35 CA231991NHGRI NIH HHS R01 HG004659NHGRI NIH HHS U01 HG009417NHGRI NIH HHS U41 HG009889NHLBI NIH HHS R01 HL137223
6 · The paper itself

Abstract

Much of the human proteome is involved in mRNA homeostasis, but most RNA-binding proteins lack chemical probes. Here we identify electrophilic small molecules that rapidly and stereoselectively decrease the expression of transcripts encoding the androgen receptor and its splice variants in prostate cancer cells. We show by chemical proteomics that the compounds engage C145 of the RNA-binding protein NONO. Broader profiling revealed that covalent NONO ligands suppress an array of cancer-relevant genes and impair cancer cell proliferation. Surprisingly, these effects were not observed in cells genetically disrupted for NONO, which were instead resistant to NONO ligands. Reintroduction of wild-type NONO, but not a C145S mutant, restored ligand sensitivity in NONO-disrupted cells. The ligands promoted NONO accumulation in nuclear foci and stabilized NONO-RNA interactions, supporting a trapping mechanism that may prevent compensatory action of paralog proteins PSPC1 and SFPQ. These findings show that NONO can be co-opted by covalent small molecules to suppress protumorigenic transcriptional networks.

Indexed as

DNA-Binding ProteinsTranscriptomeHumansMaleRNARNA-Binding ProteinsDNA-Binding ProteinsNONO protein, humanPSPC1 protein, humanRNARNA-Binding Proteins

Identifiers

PMID36864190
PMCPMC10337234
OpenAlexW4322766934

What OpenQuestion holds

Textmetadata
LicenceTDM
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.