ArticleCell reports2025
Multi-omics and biochemical reconstitution reveal CDK7-dependent mechanisms controlling RNA polymerase II function at gene 5'- and 3' ends.
Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- CDK12/13 inhibition overcomes platinum resistance by impairing RNA metabolism.Signal transduction and targeted therapy · 2026Article
- RNA polymerase II transcription initiation with and without XPB translocase activity.Communications biology · 2026Review
- Base Composition Influences the Position and Precision of RNA Polymerase II Disassociation in Basal and Perturbed Conditions.bioRxiv : the preprint server for biology · 2025Article
- Real-time visualization of reconstituted transcription reveals RNAPII activation mechanisms at single promoters.Cell reports · 2025Article
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Abstract
CDK7 regulates RNA polymerase II (RNAPII) initiation, elongation, and termination through incompletely understood mechanisms. Because contaminating kinases prevent reliable CDK7 analysis with nuclear extracts, we reconstitute RNAPII transcription with purified factors. We show that CDK7 inhibition slows and/or pauses RNAPII promoter-proximal transcription and suppresses re-initiation, and these effects are Mediator and TFIID dependent. Similarly in human cells, CDK7 inhibition reduces transcriptional output by suppressing RNAPII initiation and/or re-initiation. Moreover, widespread 3' end readthrough transcription occurs in CDK7-inhibited cells; mechanistically, this results from rapid nuclear depletion of RNAPII elongation and termination factors (e.g., DSIF, Integrator, NELF, SPT6, PPP1R10/PNUTS, and SCAF8), including high-confidence CDK7 kinase targets. Collectively, these results define how CDK7 governs RNAPII function at gene 5' ends and 3' ends and reveal that nuclear abundance of elongation and termination factors is kinase dependent. Because 3'-readthrough transcription is commonly induced during stress, our results further suggest that regulated suppression of CDK7 activity enables this transcriptional response.
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