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 using Drosophila-specific antibodies raised against recombinant GST fusion proteins expressed in E. coli.
“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
The STAR METHODS sections on antibody generation and Western blotting say that custom antibodies against Drosophila proteins were raised using recombinant proteins expressed in E. coli and that blots were probed with custom and commercial antibodies. Our copy does not identify those recombinant proteins as GST fusion proteins, and not all antibodies used for blots were raised this way. (LLM, conf=0.88)
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- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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