Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The Integrator complex terminates promoter-proximal transcription at protein-coding genes

Nathan D. Elrod, Telmo Henriques, Kai-Lieh Huang, Deirdre C. Tatomer, Jeremy E. Wilusz, Eric J. Wagner, View ORCID ProfileKaren Adelman
doi: https://doi.org/10.1101/725507
Nathan D. Elrod
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Telmo Henriques
2Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kai-Lieh Huang
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Deirdre C. Tatomer
3Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeremy E. Wilusz
3Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric J. Wagner
1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Karen_adelman@hms.harvard.edu ejwagner@utmb.edu
Karen Adelman
2Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Karen Adelman
  • For correspondence: Karen_adelman@hms.harvard.edu ejwagner@utmb.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

SUMMARY

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 25-60 nucleotide-long nascent RNA for many minutes while awaiting signals for release into the gene body. However, a number 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, 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.

Highlights

  • The Integrator complex inhibits transcription elongation at ∼15% of mRNA genes

  • Integrator targets promoter-proximally paused Pol II for termination

  • The RNA endonuclease of Integrator subunit 11 is critical for gene attenuation

  • Integrator-repressed genes are enriched in signaling and growth-responsive pathways

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted August 05, 2019.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The Integrator complex terminates promoter-proximal transcription at protein-coding genes
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
The Integrator complex terminates promoter-proximal transcription at protein-coding genes
Nathan D. Elrod, Telmo Henriques, Kai-Lieh Huang, Deirdre C. Tatomer, Jeremy E. Wilusz, Eric J. Wagner, Karen Adelman
bioRxiv 725507; doi: https://doi.org/10.1101/725507
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
The Integrator complex terminates promoter-proximal transcription at protein-coding genes
Nathan D. Elrod, Telmo Henriques, Kai-Lieh Huang, Deirdre C. Tatomer, Jeremy E. Wilusz, Eric J. Wagner, Karen Adelman
bioRxiv 725507; doi: https://doi.org/10.1101/725507

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (2440)
  • Biochemistry (4803)
  • Bioengineering (3340)
  • Bioinformatics (14724)
  • Biophysics (6658)
  • Cancer Biology (5188)
  • Cell Biology (7455)
  • Clinical Trials (138)
  • Developmental Biology (4378)
  • Ecology (6904)
  • Epidemiology (2057)
  • Evolutionary Biology (9943)
  • Genetics (7357)
  • Genomics (9550)
  • Immunology (4583)
  • Microbiology (12730)
  • Molecular Biology (4960)
  • Neuroscience (28422)
  • Paleontology (199)
  • Pathology (810)
  • Pharmacology and Toxicology (1400)
  • Physiology (2031)
  • Plant Biology (4521)
  • Scientific Communication and Education (980)
  • Synthetic Biology (1305)
  • Systems Biology (3922)
  • Zoology (731)