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

ABSTRACT: 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.

SUBMITTER: Shimada R

PROVIDER: S-EPMC8350546 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Shimada Ryuki R Koike Hiroko H Hirano Takamasa T Kato Yuzuru Y Saga Yumiko Y

iScience 20210722 8

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 <i>Nanos2</i>-KO testes and reveal ...[more]

PMID: 34401671

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