PT  - JOURNAL ARTICLE
AU  - Junaid Akhtar
AU  - Nastasja Kreim
AU  - Federico Marini
AU  - Giriram Kumar Mohana
AU  - Daniel Brune
AU  - Harald Binder
AU  - Jean-Yves Roignant
TI  - The exon junction complex regulates the release and phosphorylation of paused RNA polymerase II
AID  - 10.1101/271544
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 271544
4099  - http://biorxiv.org/content/early/2018/02/25/271544.short
4100  - http://biorxiv.org/content/early/2018/02/25/271544.full
AB  - 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) plays a critical and conserved role in 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.