TY  - JOUR
AU  - Rappe, Ulrike
AU  - Schlechter, Tanja
AU  - Aschoff, Moritz
AU  - Hotz-Wagenblatt, Agnes
AU  - Hofmann, Ilse
TI  - Nuclear ARVCF protein binds splicing factors and contributes to the regulation of alternative splicing.
JO  - The journal of biological chemistry
VL  - 289
IS  - 18
SN  - 1083-351X
CY  - Bethesda, Md.
PB  - Soc.
M1  - DKFZ-2017-02423
SP  - 12421 - 12434
PY  - 2014
AB  - 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.
KW  - ARVCF protein, human (NLM Chemicals)
KW  - Armadillo Domain Proteins (NLM Chemicals)
KW  - Cell Adhesion Molecules (NLM Chemicals)
KW  - HNRNPH2 protein, human (NLM Chemicals)
KW  - Heterogeneous-Nuclear Ribonucleoprotein Group F-H (NLM Chemicals)
KW  - Nuclear Proteins (NLM Chemicals)
KW  - Phosphoproteins (NLM Chemicals)
KW  - Protein Isoforms (NLM Chemicals)
KW  - RNA Precursors (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
KW  - RNA-Binding Proteins (NLM Chemicals)
KW  - Green Fluorescent Proteins (NLM Chemicals)
KW  - Serine-Arginine Splicing Factors (NLM Chemicals)
KW  - Ddx5 protein, human (NLM Chemicals)
KW  - DEAD-box RNA Helicases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24644279
C2  - pmc:PMC4007437
DO  - DOI:10.1074/jbc.M113.530717
UR  - https://inrepo02.dkfz.de/record/126394
ER  -