Nuclear ARVCF Protein Binds Splicing Factors and Contributes to the Regulation of Alternative Splicing
| Autor: | Agnes Hotz-Wagenblatt, Moritz Aschoff, Ilse Hofmann, Tanja Schlechter, Ulrike Rappe |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Heterogeneous nuclear ribonucleoprotein
Blotting Western Green Fluorescent Proteins Gene Expression RNA-binding protein Biology Biochemistry DEAD-box RNA Helicases Splicing factor chemistry.chemical_compound Two-Hybrid System Techniques RNA Precursors Humans Protein Isoforms RNA Messenger Nuclear protein Molecular Biology Armadillo Domain Proteins Genetics Binding Sites Microscopy Confocal Heterogeneous-Nuclear Ribonucleoprotein Group F-H Serine-Arginine Splicing Factors DDX5 Reverse Transcriptase Polymerase Chain Reaction Alternative splicing Nuclear Proteins RNA-Binding Proteins Cell Biology Phosphoproteins Alternative Splicing HEK293 Cells chemistry Armadillo repeats Mutation RNA splicing RNA Interference Caco-2 Cells Cell Adhesion Molecules Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 289:12421-12434 |
| ISSN: | 0021-9258 |
| Popis: | The armadillo repeat protein ARVCF is a component of adherens junctions. Similar to related proteins, such as p120-catenin and β-catenin, with known signaling functions, localization studies indicate a cytoplasmic and a nuclear pool of ARVCF. We find that ARVCF interacts with different proteins involved in mRNA-processing: the splicing factor SRSF1 (SF2/ASF), the RNA helicase p68 (DDX5), and the heterogeneous nuclear ribonucleoprotein hnRNP H2. All three proteins bind to ARVCF in an RNA-independent manner. Furthermore, ARVCF occurs in large RNA-containing complexes that contain both spliced and unspliced mRNAs of housekeeping genes. By domain analysis, we show that interactions occur via the ARVCF C terminus. Overexpression of ARVCF, p68, SRSF1, and hnRNP H2 induces a significant increase in splicing activity of a reporter mRNA. Upon depletion of ARVCF followed by RNA sequence analysis, several alternatively spliced transcripts are significantly changed. Therefore, we conclude that nuclear ARVCF influences splicing of pre-mRNAs. We hypothesize that ARVCF is involved in alternative splicing, generating proteomic diversity, and its deregulation may contribute to diseased states, such as cancer and neurological disorders. |
| Databáze: | OpenAIRE |
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