Format

Send to

Choose Destination
Nat Commun. 2014 Nov 20;5:5531. doi: 10.1038/ncomms6531.

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

Author information

1
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.
2
LBME-CNRS, Cell Cycle Chromatin Dynamics Laboratory. University Paul Sabatier, Toulouse 31061, France.
3
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.
4
Institute of Human Genetics, CNRS UPR1142, Laboratory of Molecular Virology; MGX-Montpellier GenomiX, 141 rue de la Cardonille, Montpellier 34396, France.
5
IGF, MGX-Montpellier GenomiX, France.
6
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.

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.

PMID:
25410209
PMCID:
PMC4263189
DOI:
10.1038/ncomms6531
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center