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

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

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 mechan...

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Main Authors: Ryuki Shimada, Hiroko Koike, Takamasa Hirano, Yuzuru Kato, Yumiko Saga
Format: Article
Language:English
Published: Elsevier 2021-08-01
Series:iScience
Subjects:
biological sciences
molecular biology
developmental biology
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004221008580
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spelling doaj-c951ec0f6d5749a5bb73d9a495689eb22021-08-22T04:30:40ZengElsevieriScience2589-00422021-08-01248102890NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cellsRyuki Shimada0Hiroko Koike1Takamasa Hirano2Yuzuru Kato3Yumiko Saga4Department 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, JapanDepartment of Genetics, SOKENDAI, Yata 1111, Mishima, Shizuoka 411-8540, JapanMammalian Development Laboratory, Department of Gene Function and Phenomics, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, JapanDepartment 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, JapanDepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004221008580biological sciencesmolecular biologydevelopmental biology
collection DOAJ
language English
format Article
sources DOAJ
author Ryuki Shimada
Hiroko Koike
Takamasa Hirano
Yuzuru Kato
Yumiko Saga
spellingShingle Ryuki Shimada
Hiroko Koike
Takamasa Hirano
Yuzuru Kato
Yumiko Saga
NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells
iScience
biological sciences
molecular biology
developmental biology
author_facet Ryuki Shimada
Hiroko Koike
Takamasa Hirano
Yuzuru Kato
Yumiko Saga
author_sort Ryuki Shimada
title NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells
title_short NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells
title_full NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells
title_fullStr NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells
title_full_unstemmed NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells
title_sort nanos2 suppresses the cell cycle by repressing mtorc1 activators in embryonic male germ cells
publisher Elsevier
series iScience
issn 2589-0042
publishDate 2021-08-01
description 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.
topic biological sciences
molecular biology
developmental biology
url http://www.sciencedirect.com/science/article/pii/S2589004221008580
work_keys_str_mv AT ryukishimada nanos2suppressesthecellcyclebyrepressingmtorc1activatorsinembryonicmalegermcells
AT hirokokoike nanos2suppressesthecellcyclebyrepressingmtorc1activatorsinembryonicmalegermcells
AT takamasahirano nanos2suppressesthecellcyclebyrepressingmtorc1activatorsinembryonicmalegermcells
AT yuzurukato nanos2suppressesthecellcyclebyrepressingmtorc1activatorsinembryonicmalegermcells
AT yumikosaga nanos2suppressesthecellcyclebyrepressingmtorc1activatorsinembryonicmalegermcells
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