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哺乳類CCR4-NOT複合体成分 CNOT9の分子生物学的・生理学的機能
https://doi.org/10.15102/1394.00001395
https://doi.org/10.15102/1394.00001395009dd488-dcc9-4c10-a0ba-e2cfdd4dada9
名前 / ファイル | ライセンス | アクション |
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Full Text (14.8 MB)
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Final Exam Abstract (42.9 kB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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公開日 | 2020-06-01 | |||||||
タイトル | ||||||||
言語 | ja | |||||||
タイトル | 哺乳類CCR4-NOT複合体成分 CNOT9の分子生物学的・生理学的機能 | |||||||
タイトル | ||||||||
言語 | en | |||||||
タイトル | Molecular and Physiological function of the mammalian CCR4-NOT subunit CNOT9 | |||||||
言語 | ||||||||
言語 | eng | |||||||
資源タイプ | ||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
資源タイプ | doctoral thesis | |||||||
ID登録 | ||||||||
ID登録 | 10.15102/1394.00001395 | |||||||
ID登録タイプ | JaLC | |||||||
アクセス権 | ||||||||
アクセス権 | open access | |||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
著者 (英) |
Sarmah, Hemanta
× Sarmah, Hemanta
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抄録 | ||||||||
内容記述タイプ | Other | |||||||
内容記述 | Messenger RNA (mRNA) decay is an indisputable component of gene expression regulation. In higher eukaryotes such as humans and mice, this process is mainly governed by a multi-subunit protein assemblage known as the CCR4-NOT complex. The complex is composed of a central scaffold CNOT1, regulatory subunits CNOT2 and CNOT3, a catalytic core consisting of CNOT6, CNOT6L, CNOT7, and CNOT8 proteins, and additional three subunits CNOT9, CNOT10, and CNOT11. In this study, I analyzed the role of subunit CNOT9 in target mRNA decay in the context of mouse embryonic development. CNOT9 knockout mice appear normal during onset of gastrulation, yet exhibit severe growth and differentiation defects during mid-late gastrulation stages (E8.5 to E9.5), accompanied by extensive cell death. Similar nature of phenotype was also observed in epiblast speci<br />fic CNOT9 deletion mutants, suggesting major contribution of epiblast lineage cells in determining knockout embryo phenotype. At the molecular level, CNOT9 is primarily localized within the cytoplasm and bridges interactions between the CCR4-NOT complex and the miRNA-RISC complex. Transcriptomic analysis identi<br />ed key determinants of gastrulation such as Nodal, Lefty1/2, Cfc-1 to be signi<br />cantly upregulated in CNOT9 KO embryos relative to controls. Among these targets, Lefty2 mRNA expression was found to be post-transcriptionally regulated by CNOT9. Reporter mRNA containing Lefty2 3'-UTR element had higher stability in cells expressing CNOT1-binding-mutant form of CNOT9, compared to cells expressing wild-type CNOT9. Finally, in-vitro experiments with CNOT9 KO embryonic stem (ES) cells further substantiated the importance of gastrulation regulation via CNOT9. | |||||||
言語 | en | |||||||
口頭試問日 | ||||||||
2020-04-15 | ||||||||
学位授与年月日 | ||||||||
学位授与年月日 | 2020-05-31 | |||||||
学位名 | ||||||||
学位名 | Doctor of Philosophy | |||||||
学位授与番号 | ||||||||
学位授与番号 | 甲第56号 | |||||||
学位授与機関 | ||||||||
学位授与機関識別子Scheme | kakenhi | |||||||
学位授与機関識別子 | 38005 | |||||||
学位授与機関名 | Okinawa Institute of Science and Technology Graduate University | |||||||
著者版フラグ | ||||||||
出版タイプ | VoR | |||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
権利 | ||||||||
権利情報 | © 2020 The Author. |