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j.stemcr.2018.05.020.pdf | 4.32 MB | Adobe PDF | 見る/開く |
タイトル: | Translational Control of Sox9 RNA by mTORC1 Contributes to Skeletogenesis |
著者: | Iezaki, Takashi Horie, Tetsuhiro Fukasawa, Kazuya Kitabatake, Makoto https://orcid.org/0000-0003-0169-8562 (unconfirmed) Nakamura, Yuka Park, Gyujin Onishi, Yuki Ozaki, Kakeru Kanayama, Takashi Hiraiwa, Manami Kitaguchi, Yuka Kaneda, Katsuyuki Manabe, Takayuki Ishigaki, Yasuhito Ohno, Mutsuhito Hinoi, Eiichi |
著者名の別形: | 北畠, 真 大野, 睦人 |
キーワード: | mTORC1 translation Sox9 undifferentiated mesenchymal cells |
発行日: | 10-Jul-2018 |
出版者: | Elsevier BV |
誌名: | Stem Cell Reports |
巻: | 11 |
号: | 1 |
開始ページ: | 228 |
終了ページ: | 241 |
抄録: | The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) regulates cellular function in various cell types. Although the role of mTORC1 in skeletogenesis has been investigated previously, here we show a critical role of mTORC1/4E-BPs/SOX9 axis in regulating skeletogenesis through its expression in undifferentiated mesenchymal cells. Inactivation of Raptor, a component of mTORC1, in limb buds before mesenchymal condensations resulted in a marked loss of both cartilage and bone. Mechanistically, we demonstrated that mTORC1 selectively controls the RNA translation of Sox9, which harbors a 5′ terminal oligopyrimidine tract motif, via inhibition of the 4E-BPs. Indeed, introduction of Sox9 or a knockdown of 4E-BP1/2 in undifferentiated mesenchymal cells markedly rescued the deficiency of the condensation observed in Raptor-deficient mice. Furthermore, introduction of the Sox9 transgene rescued phenotypes of deficient skeletal growth in Raptor-deficient mice. These findings highlight a critical role of mTORC1 in mammalian skeletogenesis, at least in part, through translational control of Sox9 RNA. |
著作権等: | © 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
URI: | http://hdl.handle.net/2433/232693 |
DOI(出版社版): | 10.1016/j.stemcr.2018.05.020 |
PubMed ID: | 30008325 |
出現コレクション: | 学術雑誌掲載論文等 |
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