| Project/Area Number |
18K06187
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 43050:Genome biology-related
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| Research Institution | National Institute of Genetics |
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Principal Investigator |
Ide Satoru 国立遺伝学研究所, 遺伝メカニズム研究系, 助教 (50534567)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | リボソームRNA遺伝子 / RNAポリメラーゼI / 希少疾患 / 液ー液相分離 / 核小体 / 遺伝疾患 / クロマチン / 神経疾患 |
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| Outline of Final Research Achievements |
The nucleolus is a nuclear body with multiphase liquid droplets for ribosomal RNA (rRNA) transcription. How rRNA transcription is regulated in the droplets remains unclear. Here, using single-molecule tracking of RNA polymerase I (Pol I) and upstream binding factor (UBF), we reveal suppression of transcription with phase separation. For transcription, active Pol I formed small clusters/condensates that constrained rDNA chromatin in the nucleolus fibrillar center (FC). Treatment with a transcription inhibitor induced Pol I to dissociate from rDNA chromatin and to move like a liquid within the nucleolar cap that transformed from the FC. Expression of a Pol I mutant associated with a craniofacial disorder inhibited transcription by competing with wild-type Pol I clusters and transforming the FC into the nucleolar cap. The cap droplet excluded an initiation factor, ensuring robust silencing. Our findings suggest a mechanism of rRNA transcription suppression via phase separation.
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| Academic Significance and Societal Importance of the Research Achievements |
臨床的な所見を有しながら通常の医療の中で診断に至ることが困難な病気が多くあり、原因もわからず、治療方法も見つからないままになっている。本研究では、次世代シークエンサーを使った遺伝性疾患ゲノム解析により同定された、タンパク質翻訳装置であるリボソーム合成に関わる因子の変異を解析した。その結果、油と水が分離する原理、いわゆる液―液相分離がリボソームの異常に起因するヒト遺伝性疾患の原因となることを明らかにした。今後このような細胞の異常や関連疾患の理解が進むことが期待される。
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