Human SAP18 mediates assembly of a splicing regulatory multiprotein complex via its ubiquitin-like fold
| Autor: | Christian Schwerk, Steffen Erkelenz, Anna Katharina Dehof, Heiner Schaal, Stephanie Rattay, Andreas Hildebrandt, Kusum Kumari Singh, Klaus Schulze-Osthoff |
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| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular Protein Folding Spliceosome Multiprotein complex RNA Splicing Molecular Sequence Data Exonic splicing enhancer Biology Models Biological Article Splicing factor Acinus medicine Humans Molecular Biology Ribonucleoprotein Base Sequence Ubiquitin RNA-Binding Proteins Molecular biology Protein Structure Tertiary Cell biology medicine.anatomical_structure Ribonucleoproteins Structural Homology Protein Multiprotein Complexes RNA splicing Spliceosomes Exon junction complex Protein Multimerization Carrier Proteins Co-Repressor Proteins HeLa Cells |
| Zdroj: | RNA. 16:2442-2454 |
| ISSN: | 1469-9001 1355-8382 |
| DOI: | 10.1261/rna.2304410 |
| Popis: | RNPS1, Acinus, and SAP18 form the apoptosis- and splicing-associated protein (ASAP) complex, which is also part of the exon junction complex. Whereas RNPS1 was originally identified as a general activator of mRNA processing, all three proteins have been found within functional spliceosomes. Both RNPS1 and Acinus contain typical motifs of splicing regulatory proteins including arginine/serine-rich domains. Due to the absence of such structural features, however, a function of SAP18 in splicing regulation is completely unknown. Here we have investigated splicing regulatory activities of the ASAP components. Whereas a full-length Acinus isoform displayed only limited splicing regulatory activity, both RNPS1 and, surprisingly, SAP18 strongly modulated splicing regulation. Detailed mutational analysis and three-dimensional modeling data revealed that the ubiquitin-like fold of SAP18 was required for efficient splicing regulatory activity. Coimmunoprecipitation and immunofluorescence experiments demonstrated that SAP18 assembles a nuclear speckle-localized splicing regulatory multiprotein complex including RNPS1 and Acinus via its ubiquitin-like fold. Our results therefore suggest a novel function of SAP18 in splicing regulation. |
| Databáze: | OpenAIRE |
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