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Structural Basis for the Recognition of Spliceosomal SmN/B/B' Proteins by the RBM5 OCRE Domain in Splicing Regulation
eLIFE
  • André Mourão, Helmholtz Zentrum München
  • Sophie Bonnal, Barcelona Institute of Science and Technology
  • Komal Soni, Helmholtz Zentrum München
  • Lisa Warner, Boise State University
  • Rémy Bordonné, Université de Montpellier
  • Juan Valcárcel, Barcelona Institute of Science and Technology
  • Michael Sattler, Helmholtz Zentrum München
Document Type
Article
Publication Date
11-29-2016
Disciplines
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.
Copyright Statement

This document was originally published in eLIFE by eLife Sciences Publications, Ltd. This work is provided under a Creative Commons Attribution 4.0 license. Details regarding the use of this work can be found at: http://creativecommons.org/licenses/by/4.0/. doi: 10.7554/eLife.14707

Citation Information
André Mourão, Sophie Bonnal, Komal Soni, Lisa Warner, et al.. "Structural Basis for the Recognition of Spliceosomal SmN/B/B' Proteins by the RBM5 OCRE Domain in Splicing Regulation" eLIFE (2016)
Available at: http://works.bepress.com/lisa-warner/8/