Citation:
Mol Cell. 2018 Nov 1;72(3):496-509.e9. doi: 10.1016/j.molcel.2018.09.033
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.
Epub:
Not Epub
Link to Publication:
https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30832-3
Organism or Cell Type:
cell culture: HeLa Flp-In T-REx KPNA1, mouse neural precursos cells (NPC)
Delivery Method:
Endo-Porter