Proteomic study identifies Aurora-A-mediated regulation of alternative splicing through multiple splicing factors

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Damodaran, Arun Prasath
• dc.contributor.author Gavard, Olivia
• dc.contributor.author Gagné, Jean-Philippe
• dc.contributor.author Rogalska, Malgorzata Ewa
• dc.contributor.author Behera, Amit K.
• dc.contributor.author Mancini, Estefanía
• dc.contributor.author Bertolin, Giulia
• dc.contributor.author Courthéoux, Thibault
• dc.contributor.author Kumari, Bandana
• dc.contributor.author Cailloce, Justine
• dc.contributor.author Méreau, Agnès
• dc.contributor.author Poirier, Guy G.
• dc.contributor.author Valcárcel, J. (Juan)
• dc.contributor.author Gonatopoulos-Pournatzis, Thomas
• dc.contributor.author Watrin, Erwan
• dc.contributor.author Prigent, Claude
• dc.date.accessioned 2025-02-07T08:08:49Z
• dc.date.available 2025-02-07T08:08:49Z
• dc.date.issued 2024
• dc.description.abstract The cell cycle regulator Aurora-A kinase presents an attractive target for cancer therapies, though its inhibition is also associated with toxic side effects. To gain a more nuanced understanding of Aurora-A function, we applied shotgun proteomics to identify 407 specific protein partners, including several splicing factors. Supporting a role in alternative splicing, we found that Aurora-A localizes to nuclear speckles, the storehouse of splicing proteins. Aurora-A interacts with and phosphorylates splicing factors both in vitro and in vivo, suggesting that it regulates alternative splicing by modulating the activity of these splicing factors. Consistently, Aurora-A inhibition significantly impacts the alternative splicing of 505 genes, with RNA motif analysis revealing an enrichment for Aurora-A interacting splicing factors. Additionally, we observed a significant positive correlation between the splicing events regulated by Aurora-A and those modulated by its interacting splicing factors. An interesting example is represented by CLK1 exon 4, which appears to be regulated by Aurora-A through SRSF3. Collectively, our findings highlight a broad role of Aurora-A in the regulation of alternative splicing.
• dc.description.sponsorship Work by C. P.'s team is supported by the University of Rennes 1, the CNRS, and the Ligue Nationale Contre le Cancer “Équipe labellisée 2014-2017” and ligue35. The PhD salary of A. P. D. and the post-doc salary of T. C are supported by the Ligue Nationale Contre le Cancer and the Bretagne region. This work is also supported by the NCI/NIH Intramural Research Program (Project ZIABC012019). Work in J. V. lab was supported by Spanish Ministry of Science and Innovation (PID2020-114630GB-100/AEI/10.13039/501100011033), EMBL Partnership and Severo Ochoa Centre of Excellence (CEX2020-001049-S, MCIN/AEI/10.13039/501100011033), and the Generalitat de Catalunya through the CERCA programme.
• dc.format.mimetype application/pdf
• dc.identifier.citation Damodaran AP, Gavard O, Gagné JP, Rogalska ME, Behera AK, Mancini E, et al. Proteomic study identifies Aurora-A-mediated regulation of alternative splicing through multiple splicing factors. J Biol Chem. 2024 Nov 17;301(1):108000. DOI: 10.1016/j.jbc.2024.108000
• dc.identifier.doi http://dx.doi.org/10.1016/j.jbc.2024.108000
• dc.identifier.issn 0021-9258
• dc.identifier.uri http://hdl.handle.net/10230/69523
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof J Biol Chem. 2024 Nov 17;301(1):108000
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-114630GB-100
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2020-001049-S
• dc.rights © 2024 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Aurora-A
• dc.subject.keyword CLK1
• dc.subject.keyword RNA
• dc.subject.keyword SR protein
• dc.subject.keyword Cancer
• dc.subject.keyword Cell cycle
• dc.subject.keyword hnRNP proteins
• dc.subject.keyword Kinase
• dc.subject.keyword Mitosis
• dc.subject.keyword Proteomics
• dc.subject.keyword Splicing
• dc.title Proteomic study identifies Aurora-A-mediated regulation of alternative splicing through multiple splicing factors
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion