ArticleNature structural & molecular biology2023
The anticancer compound JTE-607 reveals hidden sequence specificity of the mRNA 3' processing machinery.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 13 citations in OpenAlex.
- Proximity of pre-mRNA 3' end processing and transcription termination is associated with enhanced gene expression.The EMBO journal · 2026Article
- The competition between splicing and 3' processing shapes the human transcriptome.Genes & development · 2026Article
- Heat stress induces ferroptosis in intramuscular preadipocytes of Hu sheep via activation of the TNF-α/NF-κB/GPX4 signaling axis.Food chemistry. Molecular sciences · 2026Article
- Regulation of gene expression by alternative polyadenylation in health and disease.Nature reviews. Genetics · 2026Review
- Transcriptional readthrough precedes alternative splicing programs triggered in CML cells by imatinib.Science advances · 2026Article
- Modulating the cleavage and polyadenylation site: from research tools to therapeutic opportunities.RNA (New York, N.Y.) · 2026Review
- Targeting CPSF73, the mRNA 3' end processing endonuclease, moves cancer cells away from the mesenchymal state.Frontiers in immunology · 2026Article
- Transcriptional readthrough precedes alternative splicing programs triggered in CML cells by imatinib.bioRxiv : the preprint server for biology · 2025Article
- RBBP6 anchors pre-mRNA 3' end processing to nuclear speckles for efficient gene expression.Molecular cell · 2025Article
- Aberrant pre-mRNA processing in cancer.The Journal of experimental medicine · 2024Review
- Decoding biology with massively parallel reporter assays and machine learning.Genes & development · 2024Review
- Modulation of diverse biological processes by CPSF, the master regulator of mRNA 3' ends.RNA (New York, N.Y.) · 2024Review
- Cleavage and polyadenylation machinery as a novel targetable vulnerability for human cancer.Cancer gene therapy · 2024Article
- Elevated pre-mRNA 3' end processing activity in cancer cells renders vulnerability to inhibition of cleavage and polyadenylation.Nature communications · 2023Article
- Fighting pain: the structure of gabapentin and its binding site in the CaNature structural & molecular biology · 2023Article
- The Advances in Deep Learning Modeling of Polyadenylation Codes.Wiley interdisciplinary reviews. RNAReview
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
JTE-607 is an anticancer and anti-inflammatory compound and its active form, compound 2, directly binds to and inhibits CPSF73, the endonuclease for the cleavage step in pre-messenger RNA (pre-mRNA) 3' processing. Surprisingly, compound 2-mediated inhibition of pre-mRNA cleavage is sequence specific and the drug sensitivity is predominantly determined by sequences flanking the cleavage site (CS). Using massively parallel in vitro assays, we identified key sequence features that determine drug sensitivity. We trained a machine learning model that can predict poly(A) site (PAS) relative sensitivity to compound 2 and provide the molecular basis for understanding the impact of JTE-607 on PAS selection and transcription termination genome wide. We propose that CPSF73 and associated factors bind to the CS region in a sequence-dependent manner and the interaction affinity determines compound 2 sensitivity. These results have not only elucidated the mechanism of action of JTE-607, but also unveiled an evolutionarily conserved sequence specificity of the mRNA 3' processing machinery.
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