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Integrator complex regulates NELF-mediated RNA polymerase II pause/release and processivity at coding genes.

Bernd Stadelmayer1, Gaël Micas2, Adrien Gamot2

  • 11] Institute of Human Genetics, CNRS UPR1142, Laboratory of Molecular Virology; MGX-Montpellier GenomiX, 141 rue de la Cardonille, Montpellier 34396, France [2] LBME-CNRS, Cell Cycle Chromatin Dynamics Laboratory. University Paul Sabatier, Toulouse 31061, France [3] INRA, TOXALIM (Research Centre in Food Toxicology), Toulouse 31300, France [4] IGF, MGX-Montpellier GenomiX, France.

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|November 21, 2014
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Summary
This summary is machine-generated.

The Integrator complex (INTScom) regulates RNA polymerase II (RNAPII) pausing and release. Specific INTScom subunits control NELF-mediated pausing and RNAPII processivity, impacting gene expression.

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Biochemistry

Background:

  • RNA polymerase II (RNAPII) pausing after initiation is crucial for gene regulation.
  • The negative elongation factor (NELF) complex is known to induce RNAPII pausing.

Purpose of the Study:

  • To investigate the role of the Integrator complex (INTScom) in NELF-mediated RNAPII pausing and gene regulation.
  • To elucidate the specific functions of INTScom subunits in controlling RNAPII dynamics.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • Analysis of human immunodeficiency virus type 1 promoter activity.
  • Genome-wide analyses of RNAPII pausing and gene expression.

Main Results:

  • NELF interacts with INTScom subunits, RNAPII, and Spt5 in an RNA and DNA-independent manner.
  • INTScom subunits specifically control NELF-mediated RNAPII pause/release at coding genes.
  • The INTS11 catalytic subunit of INTScom is essential for RNAPII processivity and completion of mRNA synthesis.
  • INTScom target genes are enriched for specific regulatory elements.

Conclusions:

  • The Integrator complex plays a critical, previously unrecognized role in regulating RNAPII pause-release and processivity.
  • These findings reveal novel functions of INTScom in the gene expression cycle, particularly for NELF-target genes.
  • Understanding INTScom's role provides new insights into the intricate mechanisms of gene regulation.