ArticleMolecular and cellular biology2012
A quantitative high-throughput in vitro splicing assay identifies inhibitors of spliceosome catalysis.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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.
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.
Who cites it
27 citing papers in PubMed.
- A U1-U3 snRNA-snoRNA interaction couples SF3B1 mutation to chromatin-state rewiring and genome instability.bioRxiv : the preprint server for biology · 2026Article
- Integrative CRISPR Screening and RNA Analyses Discover an Essential Role for PUF60 Interactions with 3' Splice Sites in Cancer Progression.Cancer research · 2026Article
- The transrepression and transactivation roles of CtBPs in the pathogenesis of different diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- A synthetic small molecule stalls pre-mRNA splicing by promoting an early-stage U2AF2-RNA complex.Cell chemical biology · 2021Article
- Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays.Molecules (Basel, Switzerland) · 2021Review
- Article
- Identification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly.Nature communications · 2020Article
- Article
- The Role of CtBP1 in Oncogenic Processes and Its Potential as a Therapeutic Target.Molecular cancer therapeutics · 2017Review
- Article
- Modulating splicing with small molecular inhibitors of the spliceosome.Wiley interdisciplinary reviews. RNA · 2017Review
- Article
- Therapeutic targeting of splicing in cancer.Nature medicine · 2016Review
- ATPγS stalls splicing after B complex formation but prior to spliceosome activation.RNA (New York, N.Y.) · 2016Article
- Small Molecule Modulators of Pre-mRNA Splicing in Cancer Therapy.Trends in molecular medicine · 2016Review
- The Natural Product N-Palmitoyl-l-leucine Selectively Inhibits Late Assembly of Human Spliceosomes.The Journal of biological chemistry · 2015Article
- Small Molecule, NSC95397, Inhibits the CtBP1-Protein Partner Interaction and CtBP1-Mediated Transcriptional Repression.Journal of biomolecular screening · 2015Article
- Telomere dysfunction drives aberrant hematopoietic differentiation and myelodysplastic syndrome.Cancer cell · 2015Article
- Identification of small molecule inhibitors of pre-mRNA splicing.The Journal of biological chemistry · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Despite intensive research, there are very few reagents with which to modulate and dissect the mRNA splicing pathway. Here, we describe a novel approach to identify such tools, based on detection of the exon junction complex (EJC), a unique molecular signature that splicing leaves on mRNAs. We developed a high-throughput, splicing-dependent EJC immunoprecipitation (EJIPT) assay to quantitate mRNAs spliced from biotin-tagged pre-mRNAs in cell extracts, using antibodies to EJC components Y14 and eukaryotic translation initiation factor 4aIII (eIF4AIII). Deploying EJIPT we performed high-throughput screening (HTS) in conjunction with secondary assays to identify splicing inhibitors. We describe the identification of 1,4-naphthoquinones and 1,4-heterocyclic quinones with known anticancer activity as potent and selective splicing inhibitors. Interestingly, and unlike previously described small molecules, most of which target early steps, our inhibitors represented by the benzothiazole-4,7-dione, BN82685, block the second of two trans-esterification reactions in splicing, preventing the release of intron lariat and ligation of exons. We show that BN82685 inhibits activated spliceosomes' elaborate structural rearrangements that are required for second-step catalysis, allowing definition of spliceosomes stalled in midcatalysis. EJIPT provides a platform for characterization and discovery of splicing and EJC modulators.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.