Exon junction complex shapes the transcriptome by repressing recursive splicing
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 hundr...
| Autores: | , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2018 |
| País: | España |
| Recursos: | Universitat Pompeu Fabra |
| Repositório: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/42934 |
| Acesso em linha: | http://hdl.handle.net/10230/42934 http://dx.doi.org/10.1016/j.molcel.2018.09.033 |
| Access Level: | Acceso aberto |
| Palavra-chave: | RS exon Alternative splicing mechanisms Evolution Exon junction complex Gene expression Microcephaly Microexon Neurodevelopmental disorders Recursive splicing |
| Resumo: | 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. |
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