Exon junction complex shapes the transcriptome by repressing recursive splicing
journal contributionposted on 2020-07-01, 11:21 authored by Lorea Blazquez Garcia, Warren Emmett, Rupert Faraway, Jose Mario Bello Pineda, Simon Bajew, Andre Gohr, Nejc Haberman, Christopher R Sibley, Robert K Bradley, Manuel Irimia, Jernej Ule
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.
RS exonalternative splicing mechanismsevolutionexon junction complexgene expressionmicrocephalymicroexonneurodevelopmental disordersrecursive splicingAlternative SplicingAnimalsCell LineCell NucleusDrosophilaExonsHEK293 CellsHeLa CellsHumansIntronsK562 CellsMiceNuclear ProteinsRNA PrecursorsRNA Splice SitesRNA SplicingRNA, MessengerRNA-Binding ProteinsRibonucleoproteinsTranscriptomeHela CellsUle - secCS-ackGEP-ack06 Biological Sciences11 Medical and Health SciencesDevelopmental Biology