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

Bernd Stadelmayer (), Gaël Micas, Adrien Gamot, Pascal Martin, Nathalie Malirat, Slavik Koval, Raoul Raffel, Bijan Sobhian, Dany Severac, Stéphanie Rialle, Hugues Parrinello, Olivier Cuvier () and Monsef Benkirane ()
Additional contact information
Bernd Stadelmayer: Institute of Human Genetics, CNRS UPR1142, Laboratory of Molecular Virology; MGX-Montpellier GenomiX, 141 rue de la Cardonille
Gaël Micas: LBME-CNRS, Cell Cycle Chromatin Dynamics Laboratory. University Paul Sabatier
Adrien Gamot: LBME-CNRS, Cell Cycle Chromatin Dynamics Laboratory. University Paul Sabatier
Pascal Martin: LBME-CNRS, Cell Cycle Chromatin Dynamics Laboratory. University Paul Sabatier
Nathalie Malirat: Institute of Human Genetics, CNRS UPR1142, Laboratory of Molecular Virology; MGX-Montpellier GenomiX, 141 rue de la Cardonille
Slavik Koval: Institute of Human Genetics, CNRS UPR1142, Laboratory of Molecular Virology; MGX-Montpellier GenomiX, 141 rue de la Cardonille
Raoul Raffel: LBME-CNRS, Cell Cycle Chromatin Dynamics Laboratory. University Paul Sabatier
Bijan Sobhian: Institute of Human Genetics, CNRS UPR1142, Laboratory of Molecular Virology; MGX-Montpellier GenomiX, 141 rue de la Cardonille
Dany Severac: IGF, MGX-Montpellier GenomiX
Stéphanie Rialle: IGF, MGX-Montpellier GenomiX
Hugues Parrinello: IGF, MGX-Montpellier GenomiX
Olivier Cuvier: LBME-CNRS, Cell Cycle Chromatin Dynamics Laboratory. University Paul Sabatier
Monsef Benkirane: Institute of Human Genetics, CNRS UPR1142, Laboratory of Molecular Virology; MGX-Montpellier GenomiX, 141 rue de la Cardonille

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract RNA polymerase II (RNAPII) pausing/termination shortly after initiation is a hallmark of gene regulation. Here, we show that negative elongation factor (NELF) interacts with Integrator complex subunits (INTScom), RNAPII and Spt5. The interaction between NELF and INTScom subunits is RNA and DNA independent. Using both human immunodeficiency virus type 1 promoter and genome-wide analyses, we demonstrate that Integrator subunits specifically control NELF-mediated RNAPII pause/release at coding genes. The strength of RNAPII pausing is determined by the nature of the NELF-associated INTScom subunits. Interestingly, in addition to controlling RNAPII pause-release INTS11 catalytic subunit of the INTScom is required for RNAPII processivity. Finally, INTScom target genes are enriched in human immunodeficiency virus type 1 transactivation response element/NELF binding element and in a 3' box sequence required for small nuclear RNA biogenesis. Revealing these unexpected functions of INTScom in regulating RNAPII pause-release and completion of mRNA synthesis of NELF-target genes will contribute to our understanding of the gene expression cycle.

Date: 2014
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DOI: 10.1038/ncomms6531

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