Unknown,Transcriptomics,Genomics,Proteomics

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Integrator complex regulates NELF-mediated RNA Polymerase II pause/release and processivity at coding genes [RNA-seq]


ABSTRACT: RNAPII pausing/termination shortly after initiation is a hallmark of gene regulation. However, the molecular mechanisms involved are still to be uncovered. Here, we show that NELF interacts with Integrator complex subunits (INTScom) forming a stable complex with RNPII and Spt5. The interaction between NELF and INTScom subunits is RNA and DNA independent. Using both HIV-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 complex. Interestingly, in addition to controlling RNAPII pause release INTS11 catalytic subunit of the INTScom is required for the synthesis of full length mRNA. Finally, INTScom-target genes are enriched in HIV-1 TAR/ NELF-binding element and in a 3’box sequence required for snRNA biogenesis. Revealing these unexpected functions of INTScom in regulating RNAPII pausing/release and completion of mRNA synthesis of NELF-target genes will contribute to our understanding of the gene expression cycle. Genome-wide expression in HeLa cells in the absence of Integrator 11, or NELF or mock (control) depleted by strand-specific RNASeq (Illumina)

ORGANISM(S): Homo sapiens

SUBMITTER: Olivier Cuvier 

PROVIDER: E-GEOD-60585 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Stadelmayer Bernd B   Micas Gaël G   Gamot Adrien A   Martin Pascal P   Malirat Nathalie N   Koval Slavik S   Raffel Raoul R   Sobhian Bijan B   Severac Dany D   Rialle Stéphanie S   Parrinello Hugues H   Cuvier Olivier O   Benkirane Monsef M  

Nature communications 20141120


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 gene  ...[more]

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