UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Exon Junction Complex Shapes the Transcriptome by Repressing Recursive Splicing

Blazquez, L; Emmett, W; Faraway, R; Pineda, JMB; Bajew, S; Gohr, A; Haberman, N; ... Ule, J; + view all (2018) Exon Junction Complex Shapes the Transcriptome by Repressing Recursive Splicing. Molecular Cell , 72 (3) 496-509.e9. 10.1016/j.molcel.2018.09.033. Green open access

[thumbnail of LoreaBlazquez_1-s2.0-S1097276518308323-main.pdf]
Preview
Text
LoreaBlazquez_1-s2.0-S1097276518308323-main.pdf - Published Version

Download (3MB) | Preview

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.

Type: Article
Title: Exon Junction Complex Shapes the Transcriptome by Repressing Recursive Splicing
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.molcel.2018.09.033
Publisher version: https://doi.org/10.1016/j.molcel.2018.09.033
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: RS exon, alternative splicing mechanisms, evolution, exon junction complex, gene expression, microcephaly, microexon, neurodevelopmental disorders, recursive splicing
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10061487
Downloads since deposit
52Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item