Structural basis for the recognition of spliceosomal SmN/B/B’ proteins by the RBM5 OCRE domain in splicing regulation
Mostra el registre complet Registre parcial de l'ítem
- dc.contributor.author Mourão, Andréca
- dc.contributor.author Bonnal, Sophieca
- dc.contributor.author Soni, Komalca
- dc.contributor.author Warner, Lisaca
- dc.contributor.author Bordonné, Rémyca
- dc.contributor.author Valcárcel, J. (Juan)ca
- dc.contributor.author Sattler, Michaelca
- dc.date.accessioned 2017-04-20T12:09:13Z
- dc.date.available 2017-04-20T12:09:13Z
- dc.date.issued 2016
- dc.description.abstract The multi-domain splicing factor RBM5 regulates the balance between antagonistic isoforms of the apoptosis-control genes FAS/CD95, Caspase-2 and AID. An OCRE (OCtamer REpeat of aromatic residues) domain found in RBM5 is important for alternative splicing regulation and mediates interactions with components of the U4/U6.U5 tri-snRNP. We show that the RBM5 OCRE domain adopts a unique β–sheet fold. NMR and biochemical experiments demonstrate that the OCRE domain directly binds to the proline-rich C-terminal tail of the essential snRNP core proteins SmN/B/B’. The NMR structure of an OCRE-SmN peptide complex reveals a specific recognition of poly-proline helical motifs in SmN/B/B’. Mutation of conserved aromatic residues impairs binding to the Sm proteins in vitro and compromises RBM5-mediated alternative splicing regulation of FAS/CD95. Thus, RBM5 OCRE represents a poly-proline recognition domain that mediates critical interactions with the C-terminal tail of the spliceosomal SmN/B/B’ proteins in FAS/CD95 alternative splicing regulation.
- dc.description.sponsorship This work was supported by the Deutsche Forschungsgemeinschaft (DFG SFB1035, GRK1721) to MS, and by the Centre National de la Recherche Scientifique (CNRS) to RB. Work in JV’s lab is supported by Fundación Botín, by Banco de Santander through its Santander Universities Global Division and Consolider RNAREG, MICINN and AGAUR, and by the Spanish Ministry of Economy and Competitiveness ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208.
- dc.format.mimetype application/pdfca
- dc.identifier.citation Mourão A, Bonnal S, Soni K, Warner L, Bordonné R, Valcárcel J, Sattler M. Structural basis for the recognition of spliceosomal SmN/B/B’ proteins by the RBM5 OCRE domain in splicing regulation. eLife: 2016; 5: e14707. DOI: 10.7554/eLife.14707.001
- dc.identifier.doi http://dx.doi.org/10.7554/eLife.14707
- dc.identifier.issn 2050-084X
- dc.identifier.uri http://hdl.handle.net/10230/30859
- dc.language.iso eng
- dc.publisher eLifeca
- dc.relation.ispartof eLife: 2016; 5: e14707
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SEV2012-0208
- dc.rights © Copyright Mourão 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.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Alternative splicing
- dc.subject.keyword Human
- dc.subject.keyword NMR-spectroscopy
- dc.subject.keyword OCRE domain
- dc.subject.keyword Poly-proline
- dc.subject.keyword Protein-protein interactions
- dc.subject.keyword Structural biology
- dc.title Structural basis for the recognition of spliceosomal SmN/B/B’ proteins by the RBM5 OCRE domain in splicing regulationca
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion