ArticleeLife2024
Human promoter directionality is determined by transcriptional initiation and the opposing activities of INTS11 and CDK9.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- Polymerase face-off: emerging concepts in transcription-replication coordination.EMBO reports · 2026Review
- Adulthood depletion of Integrator extends lifespan and healthspan via defective pre-mRNA processing.bioRxiv : the preprint server for biology · 2026Article
- Restrictor slows RNAPII elongation to promote termination at noncoding RNA loci.Genes & development · 2025Article
- Overlapping and distinct functions of SPT6, PNUTS, and PCF11 in regulating transcription termination.Nucleic acids research · 2025Article
- DNA-directed termination of mammalian RNA polymerase II.Genes & development · 2024Article
- Article
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Authors and funding
5 authors.
Funding
Abstract
RNA polymerase II (RNAPII) transcription initiates bidirectionally at many human protein-coding genes. Sense transcription usually dominates and leads to messenger RNA production, whereas antisense transcription rapidly terminates. The basis for this directionality is not fully understood. Here, we show that sense transcriptional initiation is more efficient than in the antisense direction, which establishes initial promoter directionality. After transcription begins, the opposing functions of the endonucleolytic subunit of Integrator, INTS11, and cyclin-dependent kinase 9 (CDK9) maintain directionality. Specifically, INTS11 terminates antisense transcription, whereas sense transcription is protected from INTS11-dependent attenuation by CDK9 activity. Strikingly, INTS11 attenuates transcription in both directions upon CDK9 inhibition, and the engineered recruitment of CDK9 desensitises transcription to INTS11. Therefore, the preferential initiation of sense transcription and the opposing activities of CDK9 and INTS11 explain mammalian promoter directionality.
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Registered trials
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