Mourão, AndréBonnal, SophieSoni, KomalWarner, LisaBordonné, RémyValcárcel, J. (Juan)Sattler, Michael2017-04-202017-04-202016Mourão 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.14707.0012050-084Xhttp://hdl.handle.net/10230/30859The 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.application/pdfeng© 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.7554/eLife.14707Alternative splicingHumanNMR-spectroscopyOCRE domainPoly-prolineProtein-protein interactionsStructural biologyinfo:eu-repo/semantics/openAccess