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

Author

Listed:
  • Junaid Akhtar

    (Institute of Molecular Biology (IMB)
    Institute of Neurobiology and Developmental Biology, JGU)

  • 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))

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.

Suggested Citation

  • Junaid Akhtar & Nastasja Kreim & Federico Marini & Giriram Mohana & Daniel Brüne & Harald Binder & Jean-Yves Roignant, 2019. "Promoter-proximal pausing mediated by the exon junction complex regulates splicing," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08381-0
    DOI: 10.1038/s41467-019-08381-0
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