First Author | Ji X | Year | 2018 |
Journal | Nucleic Acids Res | Volume | 46 |
Issue | 4 | Pages | 2030-2044 |
PubMed ID | 29253178 | Mgi Jnum | J:265755 |
Mgi Id | MGI:6120389 | Doi | 10.1093/nar/gkx1255 |
Citation | Ji X, et al. (2018) PolyC-binding proteins enhance expression of the CDK2 cell cycle regulatory protein via alternative splicing. Nucleic Acids Res 46(4):2030-2044 |
abstractText | The PolyC binding proteins (PCBPs) impact alternative splicing of a subset of mammalian genes that are enriched in basic cellular functions. Here, we focus our analysis on PCBP-controlled cassette exon-splicing within the cell cycle control regulator cyclin-dependent kinase-2 (CDK2) transcript. We demonstrate that PCBP binding to a C-rich polypyrimidine tract (PPT) preceding exon 5 of the CDK2 transcript enhances cassette exon inclusion. This splice enhancement is U2AF65-independent and predominantly reflects actions of the PCBP1 isoform. Remarkably, PCBPs'' control of CDK2 ex5 splicing has evolved subsequent to mammalian divergence via conversion of constitutive exon 5 inclusion in the mouse CDK2 transcript to PCBP-responsive exon 5 alternative splicing in humans. Importantly, exclusion of exon 5 from the hCDK2 transcript dramatically represses the expression of CDK2 protein with a corresponding perturbation in cell cycle kinetics. These data highlight a recently evolved post-transcriptional pathway in primate species with the potential to modulate cell cycle control. |