Polypyrimidine tract-binding protein regulates the cell cycle through IRES-dependent translation of CDK11p58 in mouse embryonic stem cells

Abstract

Polypyrimidine tract-binding protein (PTB/PTBP1/hnRNP I) is a member of the heterogeneous nuclear ribonucleoprotein family that binds specifically to pyrimidine-rich sequences of RNAs. Although PTB is a multifunctional protein involved in RNA processing and internal ribosome entry site (IRE S)-dependent translation, the role of PTB in early mouse development is unclear. Ptb knockout mice exhibit embryonic lethality shortly after implantation and Ptb -/- embryonic stem (ES) cells have a severe proliferation defect that includes a prolonged G2/M phase. The present study shows that PTB promotes M phase progression by the direct repression of CDK11p58 IRE S activity in ES cells. The protein expression and IRE S activity of CDK11 p58 in Ptb-/- ES cells is higher than that of wild-type ES cells, indicating that PTB is involved in the repression of CDK11p58 expression through IRE S-dependent translation in ES cells. Interestingly, CDK11p58 IRE S activity is activated by upstream of N-Ras (UNR) in 293T and NIH3T3 cells, whereas UNR is not present in the Cdk11 mRNA-protein complex in ES cells. In addition, PTB interacts directly with the IRE S region of CDK11p58 in ES cells. These results suggest that PTB regulates the precise expression of CDK11p58 through direct interaction with CDK11p58 IRE S and promotes M phase progression in ES cells. © 2011 Landes Bioscience.