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Dev Cell. 2015 Jul 6;34(1):96-107. doi: 10.1016/j.devcel.2015.05.014. Epub 2015 Jun 25.

RNA Binding Protein Nanos2 Organizes Post-transcriptional Buffering System to Retain Primitive State of Mouse Spermatogonial Stem Cells.

Author information

1
Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
2
Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
3
Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
4
Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan; Department of Hematology, Stanford University School of Medicine, Stanford, CA 94305, USA.
5
Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan; Translational Cardiovascular Therapeutics, William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
6
Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan; Department of Genetics, SOKENDAI, Yata 1111, Mishima, Shizuoka 411-8540, Japan. Electronic address: ysaga@lab.nig.ac.jp.

Abstract

In many adult tissues, homeostasis relies on self-renewing stem cells that are primed for differentiation. The reconciliation mechanisms of these characteristics remain a fundamental question in stem cell biology. We propose that regulation at the post-transcriptional level is essential for homeostasis in murine spermatogonial stem cells (SSCs). Here, we show that Nanos2, an evolutionarily conserved RNA-binding protein, works with other cellular messenger ribonucleoprotein (mRNP) components to ensure the primitive status of SSCs through a dual mechanism that involves (1) direct recruitment and translational repression of genes that promote spermatogonial differentiation and (2) repression of the target of rapamycin complex 1 (mTORC1), a well-known negative pathway for SSC self-renewal, by sequestration of the core factor mTOR in mRNPs. This mechanism links mRNA turnover to mTORC1 signaling through Nanos2-containing mRNPs and establishes a post-transcriptional buffering system to facilitate SSC homeostasis in the fluctuating environment within the seminiferous tubule.

PMID:
26120033
DOI:
10.1016/j.devcel.2015.05.014
[Indexed for MEDLINE]
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