Exon junction complex shapes the transcriptome by repressing recursive splicing

Lorea Blazquez, Warren Emmett, Rupert Faraway, Jose Mario Bello Pineda, Simon Bajew, Andre Gohr, Nejc Haberman, Christopher R Sibley, Robert K Bradley, Manuel Irimia, Jernej Ule

Research output: Contribution to journalArticlepeer-review


Recursive splicing (RS) starts by defining an "RS-exon," which is then spliced to the preceding exon, thus creating a recursive 5' splice site (RS-5ss). Previous studies focused on cryptic RS-exons, and now we find that the exon junction complex (EJC) represses RS of hundreds of annotated, mainly constitutive RS-exons. The core EJC factors, and the peripheral factors PNN and RNPS1, maintain RS-exon inclusion by repressing spliceosomal assembly on RS-5ss. The EJC also blocks 5ss located near exon-exon junctions, thus repressing inclusion of cryptic microexons. The prevalence of annotated RS-exons is high in deuterostomes, while the cryptic RS-exons are more prevalent in Drosophila, where EJC appears less capable of repressing RS. Notably, incomplete repression of RS also contributes to physiological alternative splicing of several human RS-exons. Finally, haploinsufficiency of the EJC factor Magoh in mice is associated with skipping of RS-exons in the brain, with relevance to the microcephaly phenotype and human diseases.

Original languageEnglish
Pages (from-to)496-509.e9
Number of pages14
JournalMolecular Cell
Issue number3
Publication statusPublished - 1 Nov 2018


  • gene expression
  • alternative splicing mechanisms
  • recursive splicing
  • exon junction complex
  • RS exon
  • microexon
  • microcephaly
  • neurodevelopmental disorders
  • evolution


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