4a90
Crystal structure of mouse SAP18 residues 1-143
Structural highlights
FunctionSAP18_MOUSE Component of the SIN3-repressing complex. Enhances the ability of SIN3-HDAC1-mediated transcriptional repression. When tethered to the promoter, it can direct the formation of a repressive complex to core histone proteins. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP and PSAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. The ASAP complex can inhibit mRNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits the formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function (By similarity). Publication Abstract from PubMedThe ASAP complex interacts with the exon-junction complex (EJC), a messenger ribonucleoprotein complex involved in post-transcriptional regulation. The three ASAP subunits (Acinus, RNPS1 and SAP18) have been individually implicated in transcriptional regulation, pre-mRNA splicing and mRNA quality control. To shed light on the basis for and consequences of ASAP's interaction with the EJC, we have determined the 1.9-A resolution structure of a eukaryotic ASAP core complex. The RNA-recognition motif of RNPS1 binds to a conserved motif of Acinus with a recognition mode similar to that observed in splicing U2AF proteins. The Acinus-RNPS1 platform recruits the ubiquitin-like domain of SAP18, forming a ternary complex that has both RNA- and protein-binding properties. Unexpectedly, our structural analysis identified an Acinus-like motif in Pinin, another EJC-associated splicing factor. We show that Pinin physically interacts with RNPS1 and SAP18, forming an alternative ternary complex, PSAP. The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex.,Murachelli AG, Ebert J, Basquin C, Le Hir H, Conti E Nat Struct Mol Biol. 2012 Mar 4;19(4):378-86. doi: 10.1038/nsmb.2242. PMID:22388736[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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