Cited by 184Genomics and Chromatin DynamicsRNA Research and SplicingChromatin Remodeling and Cancer

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Integrator Recruits Protein Phosphatase 2A to Prevent Pause Release and Facilitate Transcription Termination

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Huang, Kai-Lieh, Jee, David, Stein, Chad B., Elrod, Nathan D., Henriques, Telmo, Mascibroda, Lauren G., Baillat, David, Russell, William K., Adelman, Karen, Wagner, Eric J.·2020·Molecular Cell

DOI 10.1016/j.molcel.2020.08.016PMC PMC7660970

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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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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: Huang, Kai-Lieh
Stein, Chad B.
Elrod, Nathan D.
Henriques, Telmo
Mascibroda, Lauren G.
Baillat, David
Russell, William K.
Adelman, Karen
Wagner, Eric J.
Venue: Molecular Cell
Publisher: Elsevier BV
Published: 2020-10
Volume: 80
Issue: 2
Pages: 345-358.e9
ISSN: 1097-2765 (ISSN-L)
DOI: 10.1016/j.molcel.2020.08.016
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 379 d)
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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Integrator Recruits Protein Phosphatase 2A to Prevent Pause Release and Facilitate Transcription Termination

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