Exon Junction Complex Shapes the Transcriptome by Repressing Recursive Splicing
Copyright policy )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 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.
- University of London United Kingdom
- University of Washington United States
- University of Edinburgh United Kingdom
- Washington State University United States
- The Francis Crick Institute United Kingdom
alternative splicing mechanisms, SNRNA, recursive splicing, Alternative splicing mechanisms, Microexon, RS exon, Mice, REMOVAL, RNA Precursors, microcephaly, PROTEIN-RNA INTERACTIONS, neurodevelopmental disorders, Neurodevelopmental disorders, SITE, Nuclear Proteins, RNA-Binding Proteins, 11 Medical And Health Sciences, Exons, exon junction complex, DROSOPHILA, Ribonucleoproteins, Microcephaly, Drosophila, Life Sciences & Biomedicine, 570, Biochemistry & Molecular Biology, Evolution, RNA Splicing, Article, Cell Line, INTRON, REVEALS, evolution, Animals, Humans, RNA, Messenger, Cell Nucleus, Science & Technology, microexon, Cell Biology, 06 Biological Sciences, Recursive splicing, CORE COMPLEX, Introns, Exon junction complex, Alternative Splicing, HEK293 Cells, gene expression, Gene expression, RNA Splice Sites, EMBRYONIC STEM-CELLS, K562 Cells, Transcriptome, Developmental Biology, HeLa Cells
alternative splicing mechanisms, SNRNA, recursive splicing, Alternative splicing mechanisms, Microexon, RS exon, Mice, REMOVAL, RNA Precursors, microcephaly, PROTEIN-RNA INTERACTIONS, neurodevelopmental disorders, Neurodevelopmental disorders, SITE, Nuclear Proteins, RNA-Binding Proteins, 11 Medical And Health Sciences, Exons, exon junction complex, DROSOPHILA, Ribonucleoproteins, Microcephaly, Drosophila, Life Sciences & Biomedicine, 570, Biochemistry & Molecular Biology, Evolution, RNA Splicing, Article, Cell Line, INTRON, REVEALS, evolution, Animals, Humans, RNA, Messenger, Cell Nucleus, Science & Technology, microexon, Cell Biology, 06 Biological Sciences, Recursive splicing, CORE COMPLEX, Introns, Exon junction complex, Alternative Splicing, HEK293 Cells, gene expression, Gene expression, RNA Splice Sites, EMBRYONIC STEM-CELLS, K562 Cells, Transcriptome, Developmental Biology, HeLa Cells
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