iScience (Aug 2021)

NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells

  • Ryuki Shimada,
  • Hiroko Koike,
  • Takamasa Hirano,
  • Yuzuru Kato,
  • Yumiko Saga

Journal volume & issue
Vol. 24, no. 8
p. 102890

Abstract

Read online

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.

Keywords