Transcriptome-wide splicing network reveals specialized regulatory functions of the core spliceosome
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- dc.contributor.author Rogalska, Malgorzata
- dc.contributor.author Mancini, Estefanía
- dc.contributor.author Bonnal, Sophie
- dc.contributor.author Gohr, André
- dc.contributor.author Dunyak, Bryan M.
- dc.contributor.author Arecco, Niccolò
- dc.contributor.author Smith, Peter
- dc.contributor.author Vaillancourt, Frédéric H.
- dc.contributor.author Valcárcel, J. (Juan)
- dc.date.accessioned 2025-02-04T12:46:51Z
- dc.date.available 2025-02-04T12:46:51Z
- dc.date.issued 2024
- dc.description.abstract The spliceosome is the complex molecular machinery that sequentially assembles on eukaryotic messenger RNA precursors to remove introns (pre-mRNA splicing), a physiologically regulated process altered in numerous pathologies. We report transcriptome-wide analyses upon systematic knock down of 305 spliceosome components and regulators in human cancer cells and the reconstruction of functional splicing factor networks that govern different classes of alternative splicing decisions. The results disentangle intricate circuits of splicing factor cross-regulation, reveal that the precise architecture of late-assembling U4/U6.U5 tri-small nuclear ribonucleoprotein (snRNP) complexes regulates splice site pairing, and discover an unprecedented division of labor among protein components of U1 snRNP for regulating exon definition and alternative 5' splice site selection. Thus, we provide a resource to explore physiological and pathological mechanisms of splicing regulation.
- dc.format.mimetype application/pdf
- dc.identifier.citation Rogalska ME, Mancini E, Bonnal S, Gohr A, Dunyak BM, Arecco N, et al. Transcriptome-wide splicing network reveals specialized regulatory functions of the core spliceosome. Science. 2024 Nov;386(6721):551-60. DOI: 10.1126/science.adn8105
- dc.identifier.doi http://dx.doi.org/10.1126/science.adn8105
- dc.identifier.issn 0036-8075
- dc.identifier.uri http://hdl.handle.net/10230/69484
- dc.language.iso eng
- dc.publisher American Association for the Advancement of Science (AAAS)
- dc.relation.ispartof Science. 2024 Nov;386(6721):551-60
- dc.rights This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science. on 2024 Nov;386(6721):551-560, DOI: 10.1126/science.adn8105.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.other RNA
- dc.subject.other Cèl·lules canceroses
- dc.title Transcriptome-wide splicing network reveals specialized regulatory functions of the core spliceosome
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/acceptedVersion