The structure of the ASAP core complex reveals the existence of a Pinin-containing PSAP complex

Nat Struct Mol Biol. 2012 Mar 4;19(4):378-86. doi: 10.1038/nsmb.2242.

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.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Cell Adhesion Molecules / chemistry*
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Co-Repressor Proteins
  • Crystallography, X-Ray
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism
  • Humans
  • Mice
  • Microtubule-Associated Proteins / chemistry*
  • Microtubule-Associated Proteins / metabolism
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Protein Binding
  • RNA-Binding Proteins
  • Ribonucleoproteins / chemistry*
  • Ribonucleoproteins / metabolism
  • Saposins / chemistry*
  • Saposins / metabolism
  • Sequence Alignment
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism

Substances

  • ACIN1 protein, human
  • Acn protein, Drosophila
  • Carrier Proteins
  • Cell Adhesion Molecules
  • Co-Repressor Proteins
  • Drosophila Proteins
  • MAP9 protein, human
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • PNN protein, human
  • PSAP protein, human
  • RNA-Binding Proteins
  • RNPS1 protein, human
  • Ribonucleoproteins
  • SAP18 protein, human
  • Sap18 protein, mouse
  • Saposins
  • Transcription Factors
  • Histone Deacetylases

Associated data

  • PDB/4A6Q
  • PDB/4A8X
  • PDB/4A90