Elucidation of molecular mechanism and universality of ribosome ubiquitin code
| Project/Area Number |
18H03977
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
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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 |
¥44,330,000 (Direct Cost: ¥34,100,000、Indirect Cost: ¥10,230,000)
Fiscal Year 2020: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2019: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2018: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
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| Keywords | 翻訳品質管理 / リボソーム動態 / ユビキチン化 / リボソーム品質管理 / ストレス応答 / クライオ電子顕微鏡 / リボソーム / E3ライゲース / クライオ 電子顕微鏡 / 品質管理 / 翻訳阻害 / クライオ電子顕微 / 異常翻訳停滞 / サブユニット解離 / プロテアソーム / 翻訳制御 / リボソーム修飾 / タンパク質分解 / リボソーム動体 / ユビキチン化制御 / 異常タンパク質分解 / 異常mRNA分解 |
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| Outline of Final Research Achievements |
Accurate gene expression is the basis of life phenomena, and its breakdown and abnormalities cause various diseases. Cells maintain the quality control mechanism RQC, which recognizes and eliminates abnormal translational elongation inhibition.
The ribosome is a significant hub during the maturation processes of protein synthesis. The quality control mechanism 18S NRD controls the quality of the ribosome. The principal investigator analyzed the molecular mechanism common to two quality control mechanisms, RQC and 18S NRD, caused by abnormal translation, and E3 ubiquitin ligase recognized a specific ribosome in a translationally arrested state and the ribosome protein. We have revealed that ubiquitination of ribosomes at specific residues plays a crucial role in determining ribosome dynamics and quality controls.
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| Academic Significance and Societal Importance of the Research Achievements |
研究代表者は、翻訳品質管理に加えmRNA安定性制御やストレス応答時における特異的リボソームユビキチン化による発現制御機構を世界に先駆けて報告し、生理機能を解析している。翻訳正確性維持機構は生命現象の基盤であり、特異的修飾によるリボソーム動態制御機構の解明は、タンパク質恒常性の維持に非常に重要であることが明確になった。正確な遺伝子発現は生命現象の根幹であり、その破綻や異常は様々な疾患の原因となる。従って本研究におけるリボソーム修飾による動態制御と発現制御機構の解明は、様々なタンパク質恒常性の異常に起因する神経変性疾患について発症の理解と創薬のの分子基盤になることは間違いないと考える。
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Report
(4 results)
Research Products
(69 results)
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[Journal Article] The nascent polypeptide in the 60S subunit determines the Rqc2-dependency of ribosomal quality control.2021
Author(s)
Mizuno, M., Ebine, S., Shounai, O., Nakajima, S., Tomomatsu, S. Ikeuchi, K., Matsuo, Y., and Inada, T.*
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Journal Title
Nucleic Acids Res.
Volume: 49(4)
Issue: 4
Pages: 2102-2113
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The Ccr4-Not complex monitors the translating ribosome for codon optimality.2020
Author(s)
Robert Buschauer*, Yoshitaka Matsuo* (*Co-first author), Takato Sugiyama, Ying-Hsin Chen, Najwa Alhusaini, Thomas Sweet, Ken Ikeuchi, Jingdong Cheng, Yasuko Matsuki, Risa Nobuta, Andrea Gilmozzi, Otto Berninghausen, Petr Tesina, Thomas Becker, Jeff Coller, Toshifumi Inada and Roland Beckmann.
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Journal Title
Science
Volume: 368
Issue: 6488
Pages: 281-281
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Sequential ubiquitination of ribosomal protein uS3 triggers the degradation of non-functional 18S rRNA.2019
Author(s)
Sugiyama, T., Li, S., Kato, M., Ikeuchi, K., Ichimura, A., Matsuo, Y. and *Inada, T.
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Journal Title
Cell Reports
Volume: 26(12)
Issue: 12
Pages: 3400-3415
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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