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

Junaid Akhtar, Nastasja Kreim, Federico Marini, Giriram Mohana, Daniel Brüne, Harald Binder and Jean-Yves Roignant ()
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Junaid Akhtar: Institute of Molecular Biology (IMB)
Nastasja Kreim: Institute of Molecular Biology (IMB)
Federico Marini: Epidemiology and Informatics (IMBEI)
Giriram Mohana: Institute of Molecular Biology (IMB)
Daniel Brüne: Institute of Molecular Biology (IMB)
Harald Binder: University of Freiburg
Jean-Yves Roignant: Institute of Molecular Biology (IMB)

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract 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.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08381-0

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DOI: 10.1038/s41467-019-08381-0

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