The DOI matches its Crossref record; 83 of the 83 references it cites were found in a registry or an index.
Integrator Recruits Protein Phosphatase 2A to Prevent Pause Release and Facilitate Transcription Termination
Open accessAbstract
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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“Blots were probed as previously described using Drosophila-specific antibodies raised against recombinant GST fusion proteins expressed in E. coli (Huang et al., 2020).”
From Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq (2022) · cites this paper as Huang et al., 2020
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Cites
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“Drosophila Integrator biochemistry Stable cell lines and nuclear extract preparation RelevantDrosophila cDNAswere cloned into a pMT-3xFLAG-puro plasmid (Elrod et al., 2019; Huang et al., 2020) following themetallothionein promotor and 3x-FLAG tag.”
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Metadata
- Authors
- Huang, K.-L., Jee, D., Stein, C. B., Elrod, N. D., Henriques, T., Mascibroda, L. G., Baillat, D., Russell, W. K., Adelman, K., & Wagner, E. J.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Harvard University (US)
- Corresponding author
- Adelman, Karen
- Wagner, Eric J.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 80
- Issue
- 2
- Pages
- 345-358.e9
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC7660970
- OpenAlex
- W3089290065
- Cited by
- 184
- References
- 83
- Citations by year
- 2026: 27 · 2025: 26 · 2024: 40 · 2023: 36 · 2022: 27 · 2021: 26 · 2020: 2
- FWCI
- 7.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Welch Foundation
- National Institute of Environmental Health Sciences
- Cancer Prevention and Research Institute of Texas
- National Institute of General Medical Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- Integrator complex, protein phosphatase 2A, RNA polymerase II, transcription termination, promoter-proximal pausing, pause release, RNA cleavage, Spt5, transcription elongation, transcriptional repression
- MeSH terms
- Amino Acid Sequence, Animals, Drosophila melanogaster, Gene Expression Regulation, Humans, Phosphorylation, Promoter Regions, Genetic, RNA Polymerase II, Substrate Specificity, Transcription Factors, Signal Transduction, Conserved Sequence, Amino Acid Motifs, Protein Subunits, Drosophila Proteins, Protein Phosphatase 2, Genetic Loci, Transcription Termination, Genetic
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