Pumilio1 and Pumilio2 coordinately control mouse growth and fertility

Highly conserved RNA-binding proteins-PUF family (Pumilio and FBF) play significant roles in embryo development and fertility in Drosophila and nematodes. Physiological roles of mammalian Pumilio family have just begun to be elucidated recently. Loss of Pum1 leads to retarded mouse growth and reduced body weight. We found that both decreased cell proliferation and increased apoptosis contribute to reduced cell number in organs of Pum1-/- mice. In absence of Pum1, Pum-binding elements (PBE) mediated translational repression of p27 was abolished and increased p27 level contributed to a delay in G1/S transition. Genetic removal of p27 in Pum1-/- mice partially recued the mouse growth phenotype. Loss of Pum1 or Pum2 or both led to a reduction in body weight and sperm count. Germ cell-specific removal of Pum1 in Pum2 knockout mice resulted in male sterility. These findings established that evolutionary conserved Pum1 and Pum2 are essential posttranscriptional regulators of normal mouse growth and fertility.