title: The DNA replication licensing factor miniature chromosome maintenance 7 is essential for RNA splicing of epidermal growth factor receptor, c-Met, and platelet-derived growth factor receptor.
abstract: Miniature chromosome maintenance 7 (MCM7) is an essential component of DNA replication licensing complex. Recent studies indicate that MCM7 is amplified and overexpressed in a variety of human malignancies. In this report, we show that MCM7 binds SF3B3. The binding motif is located in the N terminus (amino acids 221-248) of MCM7. Knockdown of MCM7 or SF3B3 significantly increased unspliced RNA of epidermal growth factor receptor, platelet-derived growth factor receptor, and c-Met. A dramatic drop of reporter gene expression of the oxytocin exon 1-intron-exon 2-EGFP construct was also identified in SF3B3 and MCM7 knockdown PC3 and DU145 cells. The MCM7 or SF3B3 depleted cell extract failed to splice reporter RNA in in vitro RNA splicing analyses. Knockdown of SF3B3 and MCM7 leads to an increase of cell death of both PC3 and DU145 cells. Such cell death induction is partially rescued by expressing spliced c-Met. To our knowledge, this is the first report suggesting that MCM7 is a critical RNA splicing factor, thus giving significant new insight into the oncogenic activity of this protein.
authors.affiliation: From the Departments of Pathology and.
authors.forename: Zhang-Hui
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: From the Departments of Pathology and.
authors.forename: Yan P
authors.initials: YP
authors.lastname: Yu
authors.affiliation: From the Departments of Pathology and.
authors.forename: George
authors.initials: G
authors.lastname: Michalopoulos
authors.affiliation: Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261.
authors.forename: Joel
authors.initials: J
authors.lastname: Nelson
authors.affiliation: From the Departments of Pathology and luoj@msx.upmc.edu.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Luo
mesh_terms: D017209:Apoptosis; D016923:Cell Death; D045744:Cell Line, Tumor; D004261:DNA Replication; D044127:Epigenesis, Genetic; D066246:ErbB Receptors / Q000378:metabolism*; D005091:Exons; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007438:Introns; D064168:Minichromosome Maintenance Complex Component 7 / Q000378:metabolism*; D010121:Oxytocin / Q000737:chemistry; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D012326:RNA Splicing; D034741:RNA, Small Interfering / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction; D017381:Spliceosomes / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D049452:Green Fluorescent Proteins; D010121:Oxytocin; D005982:Glutathione Transferase; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D020796:Receptor, Platelet-Derived Growth Factor alpha; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7
keywords: DNA Replication; Epigenetics; Oncogene; RNA; Spliceosome