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Transcriptome-wide modulation of splicing by the exon junction complex

BACKGROUND: The exon junction complex (EJC) is a dynamic multi-protein complex deposited onto nuclear spliced mRNAs upstream of exon-exon junctions. The four core proteins, eIF4A3, Magoh, Y14 and MLN51, are stably bound to mRNAs during their lifecycle, serving as a binding platform for other nuclear...

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Autores principales: Wang, Zhen, Murigneux, Valentine, Le Hir, Hervé
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268817/
https://www.ncbi.nlm.nih.gov/pubmed/25476502
http://dx.doi.org/10.1186/s13059-014-0551-7
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author Wang, Zhen
Murigneux, Valentine
Le Hir, Hervé
author_facet Wang, Zhen
Murigneux, Valentine
Le Hir, Hervé
author_sort Wang, Zhen
collection PubMed
description BACKGROUND: The exon junction complex (EJC) is a dynamic multi-protein complex deposited onto nuclear spliced mRNAs upstream of exon-exon junctions. The four core proteins, eIF4A3, Magoh, Y14 and MLN51, are stably bound to mRNAs during their lifecycle, serving as a binding platform for other nuclear and cytoplasmic proteins. Recent evidence has shown that the EJC is involved in the splicing regulation of some specific events in both Drosophila and mammalian cells. RESULTS: Here, we show that knockdown of EJC core proteins causes widespread alternative splicing changes in mammalian cells. These splicing changes are specific to EJC core proteins, as knockdown of eIF4A3, Y14 and MLN51 shows similar splicing changes, and are different from knockdown of other splicing factors. The splicing changes can be rescued by a siRNA-resistant form of eIF4A3, indicating an involvement of EJC core proteins in regulating alternative splicing. Finally, we find that the splicing changes are linked with RNA polymerase II elongation rates. CONCLUSION: Taken together, this study reveals that the coupling between EJC proteins and splicing is broader than previously suspected, and that a possible link exists between mRNP assembly and splice site recognition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0551-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-42688172014-12-17 Transcriptome-wide modulation of splicing by the exon junction complex Wang, Zhen Murigneux, Valentine Le Hir, Hervé Genome Biol Research BACKGROUND: The exon junction complex (EJC) is a dynamic multi-protein complex deposited onto nuclear spliced mRNAs upstream of exon-exon junctions. The four core proteins, eIF4A3, Magoh, Y14 and MLN51, are stably bound to mRNAs during their lifecycle, serving as a binding platform for other nuclear and cytoplasmic proteins. Recent evidence has shown that the EJC is involved in the splicing regulation of some specific events in both Drosophila and mammalian cells. RESULTS: Here, we show that knockdown of EJC core proteins causes widespread alternative splicing changes in mammalian cells. These splicing changes are specific to EJC core proteins, as knockdown of eIF4A3, Y14 and MLN51 shows similar splicing changes, and are different from knockdown of other splicing factors. The splicing changes can be rescued by a siRNA-resistant form of eIF4A3, indicating an involvement of EJC core proteins in regulating alternative splicing. Finally, we find that the splicing changes are linked with RNA polymerase II elongation rates. CONCLUSION: Taken together, this study reveals that the coupling between EJC proteins and splicing is broader than previously suspected, and that a possible link exists between mRNP assembly and splice site recognition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0551-7) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-05 2014 /pmc/articles/PMC4268817/ /pubmed/25476502 http://dx.doi.org/10.1186/s13059-014-0551-7 Text en © Wang et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Wang, Zhen
Murigneux, Valentine
Le Hir, Hervé
Transcriptome-wide modulation of splicing by the exon junction complex
title Transcriptome-wide modulation of splicing by the exon junction complex
title_full Transcriptome-wide modulation of splicing by the exon junction complex
title_fullStr Transcriptome-wide modulation of splicing by the exon junction complex
title_full_unstemmed Transcriptome-wide modulation of splicing by the exon junction complex
title_short Transcriptome-wide modulation of splicing by the exon junction complex
title_sort transcriptome-wide modulation of splicing by the exon junction complex
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268817/
https://www.ncbi.nlm.nih.gov/pubmed/25476502
http://dx.doi.org/10.1186/s13059-014-0551-7
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