The RNA-binding profile of Acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulation

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• dc.contributor.author Rodor, Julieca
• dc.contributor.author Pan, Qunca
• dc.contributor.author Blencowe, Benjamin J.ca
• dc.contributor.author Eyras Jiménez, Eduardoca
• dc.contributor.author Cáceres, Javier F.ca
• dc.date.accessioned 2017-03-31T10:45:15Z
• dc.date.available 2017-03-31T10:45:15Z
• dc.date.issued 2016
• dc.description.abstract Acinus (apoptotic chromatin condensation inducer in the nucleus) is an RNA-binding protein (RBP) originally identified for its role in apoptosis. It was later found to be an auxiliary component of the exon junction complex (EJC), which is deposited at exon junctions as a consequence of pre-mRNA splicing. To uncover the cellular functions of Acinus and investigate its role in splicing, we mapped its endogenous RNA targets using the cross-linking immunoprecipitation protocol (iCLIP). We observed that Acinus binds to pre-mRNAs, associating specifically to a subset of suboptimal introns, but also to spliced mRNAs. We also confirmed the presence of Acinus as a peripheral factor of the EJC. RNA-seq was used to investigate changes in gene expression and alternative splicing following siRNA-mediated depletion of Acinus in HeLa cells. This analysis revealed that Acinus is preferentially required for the inclusion of specific alternative cassette exons and also controls the faithful splicing of a subset of introns. Moreover, a large number of splicing changes can be related to Acinus binding, suggesting a direct role of Acinus in exon and intron definition. In particular, Acinus regulates the splicing of DFFA/ICAD transcript, a major regulator of DNA fragmentation. Globally, the genome-wide identification of RNA targets of Acinus revealed its role in splicing regulation as well as its involvement in other cellular pathways, including cell cycle progression. Altogether, this study uncovers new cellular functions of an RBP transiently associated with the EJC.
• dc.description.sponsorship J.F.C. was supported by Core funding from the Medical Research Council and by the Wellcome Trust (grant 095518/Z/11/Z). B.J.B. was supported by grants from the CIHR (Canadian Institutes of Health Research). B.J.B. holds the Banbury Chair in Medical Research at the University of Toronto. E.E. was supported by MINECO (Ministerio de Economía y Competitividad) and FEDER (Fondo Europeo de Desarrollo Regional) through grant BIO2014-52566-R, by Sandra Ibarra Foundation for Cancer, and by AGAUR (Agència de Gestió d'Ajuts Universitaris i de Recerca) through grant 2014-SGR1121.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Rodor J, Pan Q, Blencowe BJ, Eyras E, Cáceres JF. The RNA-binding profile of Acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulation. RNA. 2016;22:1411-26. DOI: 10.1261/rna.057158.116
• dc.identifier.doi http://dx.doi.org/10.1261/rna.057158.116
• dc.identifier.issn 1355-8382
• dc.identifier.uri http://hdl.handle.net/10230/28359
• dc.language.iso eng
• dc.publisher Cold Spring Harbor Laboratory Press (CSHL Press)ca
• dc.relation.ispartof RNA. 2016;22:1411-26
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2014-52566-R
• dc.rights © 2016 Rodor et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society. This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword RNA-protein interactions
• dc.subject.keyword RNA-binding proteins
• dc.subject.keyword Pre-mRNA splicing
• dc.subject.keyword Exon junction complex
• dc.subject.keyword Apoptosis
• dc.title The RNA-binding profile of Acinus, a peripheral component of the exon junction complex, reveals its role in splicing regulationca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion