The crystal structure of the Split End protein SHARP adds a new layer of complexity to proteins containing RNA recognition motifs

Article Article scientifique Article The crystal structure of the Split End protein SHARP adds a new layer of complexity to proteins containing RNA recognition motifs eng 2014 author Arieti Fabiana 688234 author Gabus Caroline 692546 author Tambalo Margherita 742395 author Huet Tiphaine 734372 author Round Adam author Thore Stéphane 683814 6742-6752 10.1093/nar/gku277 24748666 0305-1048 http://nar.oxfordjournals.org/content/early/2014/04/19/nar.gku277.full.pdf?keytype=ref&ijkey=5ioPzv0O289Rx47 The Split Ends (SPEN) protein was originally discovered in Drosophila in the late 1990s. Since then, homologous proteins have been identified in eukaryotic species ranging from plants to humans. Every family member contains three predicted RNA recognition motifs (RRMs) in the N-terminal region of the protein. We have determined the crystal structure of the region of the human SPEN homolog that contains these RRMs-the SMRT/HDAC1 Associated Repressor Protein (SHARP), at 2.0 Å resolution. SHARP is a co-regulator of the nuclear receptors. We demonstrate that two of the three RRMs, namely RRM3 and RRM4, interact via a highly conserved interface. Furthermore, we show that the RRM3-RRM4 block is the main platform mediating the stable association with the H12-H13 substructure found in the steroid receptor RNA activator (SRA), a long, non-coding RNA previously shown to play a crucial role in nuclear receptor transcriptional regulation. We determine that SHARP association with SRA relies on both single- and double-stranded RNA sequences. The crystal structure of the SHARP-RRM fragment, together with the associated RNA-binding studies, extend the repertoire of nucleic acid binding properties of RRM domains suggesting a new hypothesis for a better understanding of SPEN protein functions. Dewey 570 Swiss National Science Foundation Inosine-containing RNA: synthesis and regulation. 124909 CH Project funding Swiss National Science Foundation RNA modification: From editing to polyuridylation. 140924 CH Projects Autre Ligue Genevoise contre le Cancer, n°1011; Association for International Cancer Research n°14-0346 43 Département de biologie moléculaire 161 false Nucleic acids research 42 10 c90e6eba-da72-4763-916b-87b096dc2d2e Article (Published version) Public Nucl. Acids Res.-2014-Arieti-nar_gku277.pdf 4351276 application/pdf openAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

Title	Published in	Year	Views	Downloads

Structural studies of RNA-binding domains		2014	888	6
The crystal structure of the Split End protein SHARP adds a new layer of complexity to proteins containing RNA recognition motifs	Nucleic acids research	2014	723	362

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Arieti, Fabiana