Promoter-proximal pausing mediated by the exon junction complex regulates splicing.

Détails

ID Serval
serval:BIB_5AD427061B62
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Promoter-proximal pausing mediated by the exon junction complex regulates splicing.
Périodique
Nature communications
Auteur(s)
Akhtar J., Kreim N., Marini F., Mohana G., Brüne D., Binder H., Roignant J.Y.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
31/01/2019
Peer-reviewed
Oui
Volume
10
Numéro
1
Pages
521
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Promoter-proximal pausing of RNA polymerase II (Pol II) is a widespread transcriptional regulatory step across metazoans. Here we find that the nuclear exon junction complex (pre-EJC) is a critical and conserved regulator of this process. Depletion of pre-EJC subunits leads to a global decrease in Pol II pausing and to premature entry into elongation. This effect occurs, at least in part, via non-canonical recruitment of pre-EJC components at promoters. Failure to recruit the pre-EJC at promoters results in increased binding of the positive transcription elongation complex (P-TEFb) and in enhanced Pol II release. Notably, restoring pausing is sufficient to rescue exon skipping and the photoreceptor differentiation defect associated with depletion of pre-EJC components in vivo. We propose that the pre-EJC serves as an early transcriptional checkpoint to prevent premature entry into elongation, ensuring proper recruitment of RNA processing components that are necessary for exon definition.
Mots-clé
Animals, Cell Nucleus/genetics, Cell Nucleus/metabolism, Exons/genetics, Gene Expression Regulation/genetics, Gene Expression Regulation/physiology, HeLa Cells, Humans, Promoter Regions, Genetic/genetics, RNA Polymerase II/genetics, RNA Polymerase II/metabolism, RNA Splicing/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/10/2019 12:30
Dernière modification de la notice
29/10/2019 6:26
Données d'usage