title: Nuclear ARVCF protein binds splicing factors and contributes to the regulation of alternative splicing.
abstract: 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.
authors.affiliation: From the Division of Vascular Oncology and Metastasis, German Cancer Research Center, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Rappe
authors.forename: Tanja
authors.initials: T
authors.lastname: Schlechter
authors.forename: Moritz
authors.initials: M
authors.lastname: Aschoff
authors.forename: Agnes
authors.initials: A
authors.lastname: Hotz-Wagenblatt
authors.forename: Ilse
authors.initials: I
authors.lastname: Hofmann
mesh_terms: D017398:Alternative Splicing; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D018938:Caco-2 Cells; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012322:RNA Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068103:Serine-Arginine Splicing Factors; D020798:Two-Hybrid System Techniques
chemical_list: C411307:ARVCF protein, human; D051186:Armadillo Domain Proteins; D015815:Cell Adhesion Molecules; C116747:HNRNPH2 protein, human; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D009687:Nuclear Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D049452:Green Fluorescent Proteins; D000068103:Serine-Arginine Splicing Factors; C506749:Ddx5 protein, human; D053487:DEAD-box RNA Helicases
keywords: Adherens Junction; Alternative Splicing; Arm Repeat Protein; Catenin; Cell Junctions; Molecular Cell Biology; Post-transcriptional Gene Expression Regulation; Ribonuclear Protein (RNP)