Exon junction complex shapes the transcriptome by repressing recursive splicing

Mostra el registre complet Registre parcial de l'ítem

• 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 Martínez, 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.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.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.doi http://dx.doi.org/10.1016/j.molcel.2018.09.033
• dc.identifier.issn 1097-2765
• dc.identifier.uri http://hdl.handle.net/10230/42934
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Mol Cell. 2018; 72(3):496-509.e9
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/617837
• 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.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• 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.title Exon junction complex shapes the transcriptome by repressing recursive splicing
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion