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| Home > Publications database > Nuclear ARVCF protein binds splicing factors and contributes to the regulation of alternative splicing. |
| Home > Publications database > Nuclear ARVCF protein binds splicing factors and contributes to the regulation of alternative splicing. |
| Journal Article | DKFZ-2017-02423 |
; ; ; ;
2014
Soc.
Bethesda, Md.
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Please use a persistent id in citations: doi:10.1074/jbc.M113.530717
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.
Keyword(s): ARVCF protein, human ; Armadillo Domain Proteins ; Cell Adhesion Molecules ; HNRNPH2 protein, human ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H ; Nuclear Proteins ; Phosphoproteins ; Protein Isoforms ; RNA Precursors ; RNA, Messenger ; RNA-Binding Proteins ; Green Fluorescent Proteins ; Serine-Arginine Splicing Factors ; Ddx5 protein, human ; DEAD-box RNA Helicases
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