title: RNA Binding Protein Nanos2 Organizes Post-transcriptional Buffering System to Retain Primitive State of Mouse Spermatogonial Stem Cells.
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.
authors.affiliation: Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shirakawa
authors.affiliation: Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ohbo
authors.affiliation: 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.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sada
authors.affiliation: Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: 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.
authors.forename: Rie
authors.initials: R
authors.lastname: Saba
authors.affiliation: 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.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D051379:Mice; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D013093:Spermatogonia / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*
chemical_list: C477341:Nanos2 protein, mouse; D016601:RNA-Binding Proteins; D012313:RNA