ArticleCell2025
RNA Pol II inhibition activates cell death independently from the loss of transcription.
Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- JP-1302 inhibits RNA polymerase I transcription and induces nucleolar stress in cancer cell lines.Cell death discovery · 2026Article
- Improved spike-in normalization clarifies the relationship between active histone modifications and transcription.Nature genetics · 2026Article
- Harnessing MDM2-Mediated Targeted Degradation of Transcriptional and Epigenetic Machinery to Disrupt Oncogenic Addictions in Pediatric Sarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting CIC::DUX4 sarcoma with Minnelide in a dual recombinase-initiated genetically engineered mouse model.The Journal of clinical investigation · 2026Article
- Cis and trans regulatory mechanisms of extrachromosomal DNA segregation.Nature cell biology · 2026Article
- Single-molecule imaging reveals RNA polymerase II dynamics and TAF1-dependent promoter-proximal pause release.Nature communications · 2026Article
- Inhibition of RNA polymerase II-activating CDK9 and CDK12/13, but not of cell cycle relevant CDKs, induces apoptosis by downregulating the short-lived Bcl-2 proteins Mcl1 and Bfl1/A1.Cell death & disease · 2026Article
- Dissecting Complex Interactions Between Ferroptosis and the Proteasome.bioRxiv : the preprint server for biology · 2026Article
- Article
- A chemical-genetic interaction between PAF1 and ENL/AF9 YEATS inhibition.RSC chemical biology · 2026Article
- RNA polymerase II degradation triggered by DNA repair occurs in trans and independently of how the lesion is recognized.Nucleic acids research · 2026Article
- Transcriptome-wide mapping reveals an RNA-dependent mechanism of platinum cancer drugs.bioRxiv : the preprint server for biology · 2025Article
- Efficacy of Minnelide in a Next-Generation Dual-Recombinase Regulated Genetically Engineered Mouse Model of CIC::DUX4 Sarcoma.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
6 authors.
Funding
Abstract
RNA Pol II-mediated transcription is essential for eukaryotic life. Although loss of transcription is thought to be universally lethal, the associated mechanisms promoting cell death are not yet known. Here, we show that death following the loss of RNA Pol II activity does not result from dysregulated gene expression. Instead, it occurs in response to loss of the hypophosphorylated form of Rbp1 (also called RNA Pol IIA). Loss of RNA Pol IIA exclusively activates apoptosis, and expression of a transcriptionally inactive version of Rpb1 rescues cell viability. Using functional genomics, we identify the mechanisms driving lethality following the loss of RNA Pol IIA, which we call the Pol II degradation-dependent apoptotic response (PDAR). Using the genetic dependencies of PDAR, we identify clinically used drugs that owe their lethality to a PDAR-dependent mechanism. Our findings unveil an apoptotic signaling response that contributes to the efficacy of a wide array of anti-cancer therapies.
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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 Socratic graph.