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  • Review Article
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Gene regulation through exon junction complex modularity

Nature Structural & Molecular Biology volume 32, pages 2387–2397 (2025)Cite this article

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Abstract

The exon junction complex (EJC) begins to assemble on the spliceosome, which deposits EJCs upstream of most exon–exon junctions during pre-messenger RNA (mRNA) splicing. EJCs acquire additional alternative modules that define heterogeneous EJCs during pre-mRNA processing to mRNA in the nucleus and after mRNA export into the cytoplasm. In this Review, we discuss the mechanisms of EJC formation, the many roles of the EJC in pre-mRNA and mRNA regulation and how these roles are influenced by EJC composition.

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Fig. 1: Diagrams of the EJC core, RNPS1-EJC and CASC3-EJC and models of RNPS1-EJC assembly on the spliceosome.
Fig. 2: Mechanisms by which EJCs can actively or passively regulate pre-mRNA metabolism.
Fig. 3: EJCs promote the packaging and nuclear export of mRNAs.
Fig. 4: EJCs promote translation by interacting with the translation initiation machinery.
Fig. 5: Mechanisms by which alternative EJC constituents promote UPF1 helicase activity.

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Acknowledgements

We thank P. Boutz and X. Rambout for comments on the manuscript. Research on EJC modularity in the Maquat laboratory is funded in part by NIH R35 GM149268 to L.E.M. and NIH K99/R00 GM152790 to E.T.A.

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  1. Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA

    Elizabeth T. Abshire & Lynne E. Maquat

  2. Center for RNA Biology, University of Rochester, Rochester, NY, USA

    Elizabeth T. Abshire & Lynne E. Maquat

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  1. Elizabeth T. Abshire
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E.T.A. and L.E.M. conceived of, wrote and modified the Review. E.T.A. generated the figures with suggestions from L.E.M.

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Correspondence to Lynne E. Maquat.

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Abshire, E.T., Maquat, L.E. Gene regulation through exon junction complex modularity. Nat Struct Mol Biol 32, 2387–2397 (2025). https://doi.org/10.1038/s41594-025-01724-0

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