title: The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex.
abstract: The 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-Å 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.
authors.affiliation: Max Planck Institute of Biochemistry, Department of Structural Cell Biology, Martinsried, Germany.
authors.forename: Andrea Giovanni
authors.initials: AG
authors.lastname: Murachelli
authors.forename: Judith
authors.initials: J
authors.lastname: Ebert
authors.forename: Claire
authors.initials: C
authors.lastname: Basquin
authors.forename: Hervé
authors.initials: H
authors.lastname: Le Hir
authors.forename: Elena
authors.initials: E
authors.lastname: Conti
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D056970:Co-Repressor Proteins; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism; D004331:Drosophila melanogaster; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins / Q000737:chemistry* / Q000378:metabolism; D049231:Saposins / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: C121310:ACIN1 protein, human; C550148:Acn protein, Drosophila; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D056970:Co-Repressor Proteins; D029721:Drosophila Proteins; C505827:MAP9 protein, human; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C102646:PNN protein, human; C483345:PSAP protein, human; D016601:RNA-Binding Proteins; C084538:RNPS1 protein, human; D012261:Ribonucleoproteins; C498650:SAP18 protein, human; C498651:Sap18 protein, mouse; D049231:Saposins; D014157:Transcription Factors; D006655:Histone Deacetylases