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 hundr...

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Detalles Bibliográficos
Autores: Blazquez, Lorea, Emmett, Warren, Faraway, Rupert, Pineda, Jose Mario Bello, Bajew, Simon, 1994-, Gohr, André, Haberman, Nejc, Sibley, Christopher R., Bradley, Robert K., Irimia Martínez, Manuel, Ule, Jernej
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/42934
Acceso en línea:http://hdl.handle.net/10230/42934
http://dx.doi.org/10.1016/j.molcel.2018.09.033
Access Level:acceso abierto
Palabra clave:RS exon
Alternative splicing mechanisms
Evolution
Exon junction complex
Gene expression
Microcephaly
Microexon
Neurodevelopmental disorders
Recursive splicing
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spelling Exon junction complex shapes the transcriptome by repressing recursive splicingBlazquez, LoreaEmmett, WarrenFaraway, RupertPineda, Jose Mario BelloBajew, Simon, 1994-Gohr, AndréHaberman, NejcSibley, Christopher R.Bradley, Robert K.Irimia Martínez, ManuelUle, JernejRS exonAlternative splicing mechanismsEvolutionExon junction complexGene expressionMicrocephalyMicroexonNeurodevelopmental disordersRecursive splicingRecursive 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.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).Elsevier201920192018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/42934http://dx.doi.org/10.1016/j.molcel.2018.09.033reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésMol Cell. 2018; 72(3):496-509.e9info:eu-repo/grantAgreement/EC/FP7/617837© 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/).http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/429342026-05-29T05:05:01Z
dc.title.none.fl_str_mv Exon junction complex shapes the transcriptome by repressing recursive splicing
title Exon junction complex shapes the transcriptome by repressing recursive splicing
spellingShingle Exon junction complex shapes the transcriptome by repressing recursive splicing
Blazquez, Lorea
RS exon
Alternative splicing mechanisms
Evolution
Exon junction complex
Gene expression
Microcephaly
Microexon
Neurodevelopmental disorders
Recursive splicing
title_short Exon junction complex shapes the transcriptome by repressing recursive splicing
title_full Exon junction complex shapes the transcriptome by repressing recursive splicing
title_fullStr Exon junction complex shapes the transcriptome by repressing recursive splicing
title_full_unstemmed Exon junction complex shapes the transcriptome by repressing recursive splicing
title_sort Exon junction complex shapes the transcriptome by repressing recursive splicing
dc.creator.none.fl_str_mv Blazquez, Lorea
Emmett, Warren
Faraway, Rupert
Pineda, Jose Mario Bello
Bajew, Simon, 1994-
Gohr, André
Haberman, Nejc
Sibley, Christopher R.
Bradley, Robert K.
Irimia Martínez, Manuel
Ule, Jernej
author Blazquez, Lorea
author_facet Blazquez, Lorea
Emmett, Warren
Faraway, Rupert
Pineda, Jose Mario Bello
Bajew, Simon, 1994-
Gohr, André
Haberman, Nejc
Sibley, Christopher R.
Bradley, Robert K.
Irimia Martínez, Manuel
Ule, Jernej
author_role author
author2 Emmett, Warren
Faraway, Rupert
Pineda, Jose Mario Bello
Bajew, Simon, 1994-
Gohr, André
Haberman, Nejc
Sibley, Christopher R.
Bradley, Robert K.
Irimia Martínez, Manuel
Ule, Jernej
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv RS exon
Alternative splicing mechanisms
Evolution
Exon junction complex
Gene expression
Microcephaly
Microexon
Neurodevelopmental disorders
Recursive splicing
topic RS exon
Alternative splicing mechanisms
Evolution
Exon junction complex
Gene expression
Microcephaly
Microexon
Neurodevelopmental disorders
Recursive splicing
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/42934
http://dx.doi.org/10.1016/j.molcel.2018.09.033
url http://hdl.handle.net/10230/42934
http://dx.doi.org/10.1016/j.molcel.2018.09.033
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Mol Cell. 2018; 72(3):496-509.e9
info:eu-repo/grantAgreement/EC/FP7/617837
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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