Blazquez, L., Emmett, W., Faraway, R., Pineda, J.M.B., Bajew, S., Gohr, A., Haberman, N., Sibley, C.R., Bradley, R.K., Irimia, M., Ule, J. (2018). Exon Junction Complex Shapes the Transcriptome by Repressing Recursive Splicing.  Mol. Cell 72(3): 496--509.e9.

FBrf0240496

Research paper

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.

PMC6224609 (PMC) (EuropePMC)