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 annot...
| Authors: | ; ; ; ; ; ; ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2018 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/42934 |
| Online Access: | http://hdl.handle.net/10230/42934 http://dx.doi.org/10.1016/j.molcel.2018.09.033 |
| Access Level: | Open access |
| Keyword: | RS exon Alternative splicing mechanisms Evolution Exon junction complex Gene expression Microcephaly Microexon Neurodevelopmental disorders Recursive splicing |
| _version_ | 1878737580752633856 |
|---|---|
| author | Blazquez, Lorea |
| 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 |
| author_browse | Bajew, Simon, 1994- Blazquez, Lorea Bradley, Robert K. Emmett, Warren Faraway, Rupert Gohr, André Haberman, Nejc Irimia Martínez, Manuel Pineda, Jose Mario Bello Sibley, Christopher R. Ule, Jernej |
| 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 |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_a1fe1d0f78f2a85851bbacbe92a2ea46 |
| institution | 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) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:10230/42934 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Exon junction complex shapes the transcriptome by repressing recursive splicing 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 RS exon Alternative splicing mechanisms Evolution Exon junction complex Gene expression Microcephaly Microexon Neurodevelopmental disorders 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. 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). Elsevier http://hdl.handle.net/10230/42934 http://dx.doi.org/10.1016/j.molcel.2018.09.033 |
| 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 |
| status_str | publishedVersion |
| title | 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_short | Exon junction complex shapes the transcriptome by repressing recursive splicing |
| title_sort | Exon junction complex shapes the transcriptome by repressing recursive splicing |
| topic | RS exon Alternative splicing mechanisms Evolution Exon junction complex Gene expression Microcephaly Microexon Neurodevelopmental disorders Recursive splicing |
| topic_facet | RS exon Alternative splicing mechanisms Evolution Exon junction complex Gene expression Microcephaly Microexon Neurodevelopmental disorders Recursive splicing |
| url | http://hdl.handle.net/10230/42934 http://dx.doi.org/10.1016/j.molcel.2018.09.033 |