ArticleMolecular cell2019
The Integrator Complex Attenuates Promoter-Proximal Transcription at Protein-Coding Genes.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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Who cites it
142 citing papers in PubMed.
- Mechanisms of transcription termination across the coding and noncoding loci of the genome.Nature reviews. Molecular cell biology · 2026Review
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- Nucleotide resolution 4-thiouridine sequencing by SNU-Seq and sf4sU-Seq reveals the transcriptional responsiveness of an epigenetically primed human genome.Nucleic acids research · 2026Article
- A comparative analysis of promoter-proximal pausing reveals kinetic and distributional dimensions of variation.bioRxiv : the preprint server for biology · 2026Article
- The Promoter-Proximal Pause: A Decision Point Governing RNA Polymerase II Fate.Annual review of biochemistry · 2026Review
- Unprocessed U1 snRNAs as a biomarker of INTS11- and BRAT1-related neurodevelopmental disorders.Genome medicine · 2026Article
- Integrator subunit INTS12 links ribotoxic stress to transcription-coupled nucleotide excision repair.Nature structural & molecular biology · 2026Article
- Direct roles of long non-coding RNAs in transcription activation.Nature structural & molecular biology · 2026Review
- SETD2 methyltransferase activity promotes correct transcription initiation and termination.EMBO reports · 2026Article
- Adulthood depletion of Integrator extends lifespan and healthspan via defective pre-mRNA processing.bioRxiv : the preprint server for biology · 2026Article
- Maternal IntS11 primes embryonic totipotency by organizing early zygotic transcription initiation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Integrator 20th anniversary: a molecular machine indispensable in development and disease.Trends in molecular medicine · 2026Review
- Scaling perturbations: beyond genome-scale CRISPR screens.bioRxiv : the preprint server for biology · 2026Article
- INTS1 is required for maintaining accurate transcriptional integrity and behavior in zebrafish.NAR genomics and bioinformatics · 2025Article
- Transcription quality control at the promoter-proximal checkpoint.Genes & development · 2025Review
- Defining the roles of the Integrator, NEXT, and nuclear exosome complexes in Drosophila oogenesis.Cell reports · 2025Article
- Identification of human RNA Polymerase II interactors at early stages of transcription.bioRxiv : the preprint server for biology · 2025Article
- Restrictor slows RNAPII elongation to promote termination at noncoding RNA loci.Genes & development · 2025Article
- Structure of a transcribing Pol II-DSIF-SPT6-U1 snRNP complex.Nature communications · 2025Article
- Cell-cycle-regulated transcriptional pausing ofMolecular biology of the cell · 2025Article
82 more citing papers are in PubMed but not listed here.
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7 authors.
Funding
Abstract
The transition of RNA polymerase II (Pol II) from initiation to productive elongation is a central, regulated step in metazoan gene expression. At many genes, Pol II pauses stably in early elongation, remaining engaged with the 25- to 60-nt-long nascent RNA for many minutes while awaiting signals for release into the gene body. However, 15%-20% of genes display highly unstable promoter Pol II, suggesting that paused polymerase might dissociate from template DNA at these promoters and release a short, non-productive mRNA. Here, we report that paused Pol II can be actively destabilized by the Integrator complex. Specifically, we present evidence that Integrator utilizes its RNA endonuclease activity to cleave nascent RNA and drive termination of paused Pol II. These findings uncover a previously unappreciated mechanism of metazoan gene repression, akin to bacterial transcription attenuation, wherein promoter-proximal Pol II is prevented from entering productive elongation through factor-regulated termination.
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