NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells
Ryuki Shimada,
Hiroko Koike,
Takamasa Hirano,
Yuzuru Kato,
Yumiko Saga
Affiliations
Ryuki Shimada
Department of Genetics, SOKENDAI, Yata 1111, Mishima, Shizuoka 411-8540, Japan; Mammalian Development Laboratory, Department of Gene Function and Phenomics, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan
Hiroko Koike
Department of Genetics, SOKENDAI, Yata 1111, Mishima, Shizuoka 411-8540, Japan
Takamasa Hirano
Mammalian Development Laboratory, Department of Gene Function and Phenomics, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan
Yuzuru Kato
Department of Genetics, SOKENDAI, Yata 1111, Mishima, Shizuoka 411-8540, Japan; Mammalian Development Laboratory, Department of Gene Function and Phenomics, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan
Yumiko Saga
Department of Genetics, SOKENDAI, Yata 1111, Mishima, Shizuoka 411-8540, Japan; Mammalian Development Laboratory, Department of Gene Function and Phenomics, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan; Division for the Development of Genetically Engineered Mouse Resources, Genetic Resource Center, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan; Corresponding author
Summary: During murine germ cell development, male germ cells enter the mitotically arrested G0 stage, which is an initial step of sexually dimorphic differentiation. The male-specific RNA-binding protein NANOS2 has a key role in suppressing the cell cycle in germ cells. However, the detailed mechanism of how NANOS2 regulates the cell cycle remains unclear. Using single-cell RNA sequencing (scRNA-seq), we extracted the cell cycle state of each germ cell in wild-type and Nanos2-KO testes and revealed that Nanos2 expression starts in mitotic cells and induces mitotic arrest. We identified Rheb, a regulator of mTORC1, and Ptma as possible targets of NANOS2. We propose that repression of the cell cycle is a primary function of NANOS2 and that it is mediated via the suppression of mTORC1 activity through the repression of Rheb in a post-transcriptional manner.
