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Splicing repression allows the gradual emergence of new Alu-exons in primate evolution

Attig, J; Mozos, IRDL; Haberman, N; Wang, Z; Emmett, W; Zarnack, K; Konig, J; (2016) Splicing repression allows the gradual emergence of new Alu-exons in primate evolution. eLife , 5 , Article e19. 10.7554/eLife.19545. Green open access

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Abstract

Alu elements are retrotransposons that frequently form new exons during primate evolution. Here, we assess the interplay of splicing repression by hnRNPC and nonsense-mediated mRNA decay (NMD) in the quality control and evolution of new Alu-exons. We identify 3100 new Alu-exons and show that NMD more efficiently recognises transcripts with Alu-exons compared to other exons with premature termination codons. However, some Alu-exons escape NMD, especially when an adjacent intron is retained, highlighting the importance of concerted repression by splicing and NMD. We show that evolutionary progression of 3’ splice sites is coupled with longer repressive uridine tracts. Once the 3’ splice site at ancient Alu-exons reaches a stable phase, splicing repression by hnRNPC decreases, but the exons generally remain sensitive to NMD. We conclude that repressive motifs are strongest next to cryptic exons and that gradual weakening of these motifs contributes to the evolutionary emergence of new alternative exons.

Type: Article
Title: Splicing repression allows the gradual emergence of new Alu-exons in primate evolution
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.19545
Publisher version: http://dx.doi.org/10.7554/eLife.19545
Language: English
Additional information: © Copyright Attig et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Keywords: Life Sciences & Biomedicine - Other Topics, NONSENSE-MEDIATED DECAY, MESSENGER-RNA DECAY, TRANSPOSABLE ELEMENTS, NUCLEAR RETENTION, INTRON RETENTION, HNRNP C, ACCELERATING FACTOR, TERMINATION-CODON, STEM-CELL, GENES
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/1530669
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