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Integrator is a global promoter-proximal termination complex.

Eric J Wagner1, Liang Tong2, Karen Adelman3

  • 1Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA.

Molecular Cell
|January 12, 2023
PubMed
Summary

The Integrator complex terminates transcription by RNA polymerase II (RNAPII) in metazoans. It uses dual enzymatic activities to cleave RNA and remove pause-release phosphorylation, impacting gene regulation and human health.

Keywords:
Integratorattenuationelongation controlgene regulationpolymerase pausingtranscription termination

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Structural Biology

Background:

  • Integrator is a metazoan-specific protein complex.
  • It plays a crucial role in terminating transcription at RNAPII-transcribed loci.
  • Its precise mechanisms and regulatory roles are areas of active research.

Purpose of the Study:

  • To review current knowledge on Integrator complex assembly and activity.
  • To elucidate the role of Integrator-mediated termination in gene regulation.
  • To highlight the significance of Integrator for human health.

Main Methods:

  • Structural biology studies revealing Integrator architecture.
  • Functional genomics and biochemical studies.
  • Review of existing literature on Integrator function.

Main Results:

  • Integrator recognizes paused RNAPII at promoters.
  • It employs endonuclease and protein phosphatase activities for premature termination.
  • Structural insights reveal coordinated module function for effective termination.

Conclusions:

  • Integrator-mediated termination is essential for regulating both protein-coding and noncoding genes.
  • Understanding Integrator's assembly and activity is key to comprehending gene regulation.
  • The complex holds significant implications for human health.