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 [RNA]

November 25th, 2014 by Chen, Z.-H., Yu, Y. P., Michalopoulos, G., Nelson, J., Luo, J.-H.

Miniature chromosome maintenance 7 (MCM7) is an essential component of DNA replication licensing complex. Recent studies indicate that MCM7 is amplified and over-expressed in a variety of human malignancies. In this report, we showed that MCM7 binds SF3B3. The binding motif is located in the N-terminus (aa221-248) of MCM7. Knocked-down of MCM7 or SF3B3 significantly increased unspliced RNA of epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR) and c-met. Dramatic drop of reporter gene expression of oxytocin exon1-intron-exon2-EGFP construct was also identified in SF3B3 and MCM7 knocked-down PC3 and DU145 cells. The MCM7 or SF3B3 depleted cell extract failed to splice reporter RNA in in vitro RNA splicing analyses. Knock-down of SF3B3 and MCM7 leads to 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, and thus give significant new insight into the oncogenic activity of this protein.
  • Posted in Journal of Biological Chemistry, Publications
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