Structural Basis for the Recognition of Spliceosomal SmN/B/B' Proteins by the RBM5 OCRE Domain in Splicing Regulation

Authors

André Mourão, Helmholtz Zentrum München
Sophie Bonnal, Barcelona Institute of Science and Technology
Komal Soni, Helmholtz Zentrum München
Lisa Warner, Boise State UniversityFollow
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

DOI

http://dx.doi.org/10.7554/eLife.14707

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

Publication Information

Mourão, André; Bonnal, Sophie; Soni, Komal; Warner, Lisa; Bordonné, Rémy; Valcárcel, Juan; and Sattler, Michael. (2016). "Structural Basis for the Recognition of Spliceosomal SmN/B/B' Proteins by the RBM5 OCRE Domain in Splicing Regulation". eLIFE, e14707-1 - e14707-12.