Abstract
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 language | English |
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Pages (from-to) | 496-509.e9 |
Number of pages | 14 |
Journal | Molecular Cell |
Volume | 72 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Nov 2018 |
Keywords
- gene expression
- alternative splicing mechanisms
- recursive splicing
- exon junction complex
- RS exon
- microexon
- microcephaly
- neurodevelopmental disorders
- evolution
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Chris Sibley
- School of Biological Sciences - Sir Henry Dale Fellow
- Edinburgh Neuroscience
Person: Academic: Research Active