title: Integrator complex regulates NELF-mediated RNA polymerase II pause/release and processivity at coding genes.
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.
authors.affiliation: 1] 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.
authors.forename: Bernd
authors.initials: B
authors.lastname: Stadelmayer
authors.affiliation: LBME-CNRS, Cell Cycle Chromatin Dynamics Laboratory. University Paul Sabatier, Toulouse 31061, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Micas
authors.affiliation: LBME-CNRS, Cell Cycle Chromatin Dynamics Laboratory. University Paul Sabatier, Toulouse 31061, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Gamot
authors.affiliation: 1] LBME-CNRS, Cell Cycle Chromatin Dynamics Laboratory. University Paul Sabatier, Toulouse 31061, France [2] INRA, TOXALIM (Research Centre in Food Toxicology), Toulouse 31300, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Martin
authors.affiliation: Institute of Human Genetics, CNRS UPR1142, Laboratory of Molecular Virology; MGX-Montpellier GenomiX, 141 rue de la Cardonille, Montpellier 34396, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Malirat
authors.affiliation: Institute of Human Genetics, CNRS UPR1142, Laboratory of Molecular Virology; MGX-Montpellier GenomiX, 141 rue de la Cardonille, Montpellier 34396, France.
authors.forename: Slavik
authors.initials: S
authors.lastname: Koval
authors.affiliation: LBME-CNRS, Cell Cycle Chromatin Dynamics Laboratory. University Paul Sabatier, Toulouse 31061, France.
authors.forename: Raoul
authors.initials: R
authors.lastname: Raffel
authors.affiliation: Institute of Human Genetics, CNRS UPR1142, Laboratory of Molecular Virology; MGX-Montpellier GenomiX, 141 rue de la Cardonille, Montpellier 34396, France.
authors.forename: Bijan
authors.initials: B
authors.lastname: Sobhian
authors.affiliation: IGF, MGX-Montpellier GenomiX, France.
authors.forename: Dany
authors.initials: D
authors.lastname: Severac
authors.affiliation: IGF, MGX-Montpellier GenomiX, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rialle
authors.affiliation: IGF, MGX-Montpellier GenomiX, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Parrinello
authors.affiliation: 1] LBME-CNRS, Cell Cycle Chromatin Dynamics Laboratory. University Paul Sabatier, Toulouse 31061, France [2] INRA, TOXALIM (Research Centre in Food Toxicology), Toulouse 31300, France [3] IGF, MGX-Montpellier GenomiX, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cuvier
authors.affiliation: 1] 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.
authors.forename: Monsef
authors.initials: M
authors.lastname: Benkirane
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D004722:Endoribonucleases; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D021122:Protein Subunits / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D035602:Transcriptional Elongation Factors / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D012097:Repressor Proteins; C481011:SUPT4H1 protein, human; C112224:SUPT5H protein, human; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; C118437:negative elongation factor; D012319:RNA Polymerase II; D004722:Endoribonucleases; C505818:INTS11 protein, human