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

Bernd Stadelmayer (1, 2, 3, 4) , Gaël Micas (5) , Adrien Gamot (5) , Pascal G.P. Martin (6, 4) , Nathalie Malirat (3, 2) , Slavik Koval (3, 2) , Raoul Raffel (5) , Bijan Sobhian (3, 2) , Dany Severac (2) , Stéphanie Rialle (2) , Hugues Parrinello (2) , Olivier Cuvier (1, 2, 4) , Monsef Benkirane (1, 2, 3, 4)

1 INRA - Institut National de la Recherche Agronomique
2 IGF MGX - Institut de Génomique Fonctionnelle - Montpellier GenomiX
3 IGH - Institut de génétique humaine
4 UT3 - Université Toulouse III - Paul Sabatier
5 LBME-CNRS - Cell Cycle Chromatin Dynamics Laboratory
6 ToxAlim - ToxAlim

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.

Mots clés: P-TEFB; 3' END; DSIF; participate; initiation; negative elongation-factor; phosphorylation; snRNA genes

Mots clés: transcription elongation; dna-damage response

Domaines: Autre [q-bio.OT]

Bernd Stadelmayer, Gaël Micas, Adrien Gamot, Pascal G.P. Martin, Nathalie Malirat, et al.. Integrator complex regulates NELF-mediated RNA polymerase II pause/release and processivity at coding genes. Nature Communications, 2014, 5, pp.5531. ⟨10.1038/ncomms6531⟩. ⟨hal-02641024⟩