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Exon junction complex shapes the transcriptome by repressing recursive splicing

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dc.contributor.author Blazquez, Lorea
dc.contributor.author Emmett, Warren
dc.contributor.author Faraway, Rupert
dc.contributor.author Pineda, Jose Mario Bello
dc.contributor.author Bajew, Simon, 1994-
dc.contributor.author Gohr, André
dc.contributor.author Haberman, Nejc
dc.contributor.author Sibley, Christopher R.
dc.contributor.author Bradley, Robert K.
dc.contributor.author Irimia, Manuel
dc.contributor.author Ule, Jernej
dc.date.accessioned 2019-11-22T08:54:21Z
dc.date.available 2019-11-22T08:54:21Z
dc.date.issued 2018
dc.identifier.citation Blazquez L, Emmett W, Faraway R, Pineda JMB, Bajew S, Gohr A, Haberman N, Sibley CR, Bradley RK, Irimia M, Ule J. Exon junction complex shapes the transcriptome by repressing recursive splicing. Mol Cell. 2018; 72(3):496-509.e9. DOI 10.1016/j.molcel.2018.09.033
dc.identifier.issn 1097-2765
dc.identifier.uri http://hdl.handle.net/10230/42934
dc.description.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.
dc.description.sponsorship This work was supported by the European Research Council (617837-Translate), the Wellcome Trust (103760/Z/14/Z), Marie Curie Intraeuropean Fellowship (627783-NeuroCRYSP) to L.B, and the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001002), the UK Medical Research Council (FC001002, MR/N013867/1), and the Wellcome Trust (FC001002).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Mol Cell. 2018; 72(3):496-509.e9
dc.rights © 2018 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Exon junction complex shapes the transcriptome by repressing recursive splicing
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.molcel.2018.09.033
dc.subject.keyword RS exon
dc.subject.keyword Alternative splicing mechanisms
dc.subject.keyword Evolution
dc.subject.keyword Exon junction complex
dc.subject.keyword Gene expression
dc.subject.keyword Microcephaly
dc.subject.keyword Microexon
dc.subject.keyword Neurodevelopmental disorders
dc.subject.keyword Recursive splicing
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/617837
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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