ArticleNature chemical biology2020
CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing's sarcoma.
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 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
50 citing papers in PubMed, 87 citations in OpenAlex.
- Proximity of pre-mRNA 3' end processing and transcription termination is associated with enhanced gene expression.The EMBO journal · 2026Article
- The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026Review
- Molecular modeling of 7-propanamide benzoxaboroles as CPSF3 inhibitors through docking-based 3D-QSAR and molecular dynamics simulations.RSC advances · 2026Article
- The competition between splicing and 3' processing shapes the human transcriptome.Genes & development · 2026Article
- Transcription termination counteracts DNA damage after WEE1 inhibition.Nucleic acids research · 2026Article
- Systematic fusion transcript discovery in mantle cell lymphoma using long-read sequencing.bioRxiv : the preprint server for biology · 2026Article
- Targeting CPSF73, the mRNA 3' end processing endonuclease, moves cancer cells away from the mesenchymal state.Frontiers in immunology · 2026Article
- The prognostic value and functional role of CPSF3 in hepatocellular carcinoma.Scientific reports · 2025Article
- Loss of CFIm activates YAP/TAZ and connects mRNA cleavage and polyadenylation inhibition to BRCAness.bioRxiv : the preprint server for biology · 2025Article
- Comprehensive investigation identifies CPSF3 as a novel prognostic and oncogenic biomarker in bladder cancer.Discover oncology · 2025Article
- Pseudokinase TRIB3 stabilizes SSRP1 via USP10-mediated deubiquitination to promote multiple myeloma progression.Oncogene · 2025Article
- CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells.Cell reports · 2025Article
- Looping forward: exploring R-loop processing and therapeutic potential.FEBS letters · 2025Review
- Aberrant pre-mRNA processing in cancer.The Journal of experimental medicine · 2024Review
- Modulation of diverse biological processes by CPSF, the master regulator of mRNA 3' ends.RNA (New York, N.Y.) · 2024Review
- A promising natural product in diffuse large B-cell lymphoma therapy by targeting PIM1.Annals of hematology · 2024Article
- Cleavage and polyadenylation machinery as a novel targetable vulnerability for human cancer.Cancer gene therapy · 2024Article
- Cell-active small molecule inhibitors validate the SNM1A DNA repair nuclease as a cancer target.Chemical science · 2024Article
- RBBP6 maintains glioblastoma stem cells through CPSF3-dependent alternative polyadenylation.Cell discovery · 2024Article
- Splicing targeting drugs highlight intron retention as an actionable vulnerability in advanced prostate cancer.Journal of experimental & clinical cancer research : CR · 2024Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
42 authors at 6 institutions in 4 countries.
Funding
Abstract
The post-genomic era has seen many advances in our understanding of cancer pathways, yet resistance and tumor heterogeneity necessitate multiple approaches to target even monogenic tumors. Here, we combine phenotypic screening with chemical genetics to identify pre-messenger RNA endonuclease cleavage and polyadenylation specificity factor 3 (CPSF3) as the target of JTE-607, a small molecule with previously unknown target. We show that CPSF3 represents a synthetic lethal node in a subset of acute myeloid leukemia (AML) and Ewing's sarcoma cancer cell lines. Inhibition of CPSF3 by JTE-607 alters expression of known downstream effectors in AML and Ewing's sarcoma lines, upregulates apoptosis and causes tumor-selective stasis in mouse xenografts. Mechanistically, it prevents the release of newly synthesized pre-mRNAs, resulting in read-through transcription and the formation of DNA-RNA hybrid R-loop structures. This study implicates pre-mRNA processing, and specifically CPSF3, as a druggable target providing an avenue to therapeutic intervention in cancer.
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.