tailieunhanh - Báo cáo khoa học: Polypyrimidine tract-binding protein is essential for early mouse development and embryonic stem cell proliferation

Polypyrimidine tract-binding protein (PTB) is a widely expressed RNA-binding protein with multiple roles in RNA processing, including the splic-ing of alternative exons, mRNA stability, mRNA localization, and internal ribosome entry site-dependent translation. Although it has been reported that increased expression of PTB is correlated with cancer cell growth, the role of PTB in mammalian development is still unclear. | Polypyrimidine tract-binding protein is essential for early mouse development and embryonic stem cell proliferation Masaki Shibayama Satona Ohno Takashi Osaka Reiko Sakamoto Akinori Tokunaga Yuhki Nakatake Mitsuharu Sato and Nobuaki Yoshida Laboratory of DevelopmentalGenetics Center for ExperimentalMedicine and Systems Biology Institute of MedicalScience University of Tokyo Japan Keywords cell cycle embryonic stem cells knockout mouse polypyrimidine tract-binding protein proliferation Correspondence N. Yoshida Laboratory of Developmental Genetics Center for ExperimentalMedicine and Systems Biology Institute of Medical Science University of Tokyo 4-6-1 Shirokanedai Minato-ku Tokyo 108-8639 Japan Fax 81 3 5449 5455 Tel 81 3 5449 5753 E-mail nobuaki@ These authors contributed equally to this work Polypyrimidine tract-binding protein PTB is a widely expressed RNA-binding protein with multiple roles in RNA processing including the splicing of alternative exons mRNA stability mRNA localization and internal ribosome entry site-dependent translation. Although it has been reported that increased expression of PTB is correlated with cancer cell growth the role of PTB in mammalian development is still unclear. Here we report that a homozygous mutation in the mouse Ptb gene causes embryonic lethality shortly after implantation. We also established Ptb ỵ embryonic stem ES cell lines and found that these mutant cells exhibited severe defects in cell proliferation without aberrant differentiation in vitro or in vivo. Furthermore cell cycle analysis and a cell synchronization assay revealed that Ptb ỵ ES cells have a prolonged G2 M phase. Thus our data indicate that PTB is essential for early mouse development and ES cell proliferation. Received 15 July 2009 revised 11 September 2009 accepted 15 September 2009 doi Introduction Mouse embryonic stem ES cells are established from the inner cell mass ICM of blastocysts. ES cells are .