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Mourao, 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 5:e14707 (2016)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
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 b–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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Candidate Tumor-suppressor; Crystal-structure; Exon Definition; Fas Molecule; U1 Snrnp; Rna; Nmr; Apoptosis; Core; Expression
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Journal eLife
Quellenangaben Volume: 5, Issue: , Pages: , Article Number: e14707 Supplement: ,
Publisher eLife Sciences Publications
Publishing Place Cambridge
Reviewing status Peer reviewed