ArticleMolecular cell2020
Integrator Recruits Protein Phosphatase 2A to Prevent Pause Release and Facilitate Transcription Termination.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 175 citations in OpenAlex.
- RNA polymerase II phosphorylation dynamics: from molecular mechanisms to human disease.RNA biology · 2026Review
- Phosphoproteomic dysregulation promotes tumor proliferation in Cushing's disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- The molecular basis of transcription initiation by RNA polymerase II.Nature reviews. Molecular cell biology · 2026Review
- Nuclear-targeted GDOWN1 potently suppresses tumors by inducing premature transcription termination and exporting Pol Ⅱ CTD phosphatases to activate RB.Cell death and differentiation · 2026Article
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- Multisite Threonine Phosphorylation in the SPT5 C-Terminal Region 1 Enables Sequence-Dependent Regulation without Global Structural Remodeling.The journal of physical chemistry. B · 2026Article
- 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
- CTDP1 governs a Pol II phosphorylation intermediate and coordinates Mediator recruitment, transcription efficiency, and splicing.Nucleic acids research · 2026Article
- Single-molecule imaging reveals RNA polymerase II dynamics and TAF1-dependent promoter-proximal pause release.Nature communications · 2026Article
- The Protein Phosphatase Inhibitor LB100 Targets the Mesenchymal Lineage of Pancreatic Ductal Adenocarcinoma.MedComm · 2026Article
- The Promoter-Proximal Pause: A Decision Point Governing RNA Polymerase II Fate.Annual review of biochemistry · 2026Review
- G0 or no-G0: phosphatase control of quiescence and cell cycle entry.Biochemical Society transactions · 2026Review
- Gene variants in periventricular nodular heterotopia.Acta epileptologica · 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
- Integrator 20th anniversary: a molecular machine indispensable in development and disease.Trends in molecular medicine · 2026Review
- PP2A activation targets MYCN in neuroblastoma.Cell death & disease · 2026Article
- Transcription quality control at the promoter-proximal checkpoint.Genes & development · 2025Review
59 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Efficient release of promoter-proximally paused RNA Pol II into productive elongation is essential for gene expression. Recently, we reported that the Integrator complex can bind paused RNA Pol II and drive premature transcription termination, potently attenuating the activity of target genes. Premature termination requires RNA cleavage by the endonuclease subunit of Integrator, but the roles of other Integrator subunits in gene regulation have yet to be elucidated. Here we report that Integrator subunit 8 (IntS8) is critical for transcription repression and required for association with protein phosphatase 2A (PP2A). We find that Integrator-bound PP2A dephosphorylates the RNA Pol II C-terminal domain and Spt5, preventing the transition to productive elongation. Thus, blocking PP2A association with Integrator stimulates pause release and gene activity. These results reveal a second catalytic function associated with Integrator-mediated transcription termination and indicate that control of productive elongation involves active competition between transcriptional kinases and phosphatases.
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Registered trials
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 OpenQuestion graph.