Physiological role of mitochondrial tRNA modification
Project/Area Number |
15K08178
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General physiology
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Research Institution | Kumamoto University |
Principal Investigator |
Wei Fan-Yan 熊本大学, 大学院生命科学研究部(医), 准教授 (90555773)
|
Research Collaborator |
Mohri Satoshi
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 代謝 / ミトコンドリア / RNA / 修飾 / RNA修飾 / エネルギー代謝 / tRNA / 翻訳 |
Outline of Final Research Achievements |
In this study, we report that Cdk5 regulatory subunit-associated protein 1 (Cdk5rap1) is responsible for 2-methylthio (ms2) modifications of mammalian mt-tRNAs for Ser(UCN), Phe, Tyr and Trp codons. Deficiency in ms2 modification markedly impaired mitochondrial protein synthesis, which resulted in respiratory defects in Cdk5rap1 knockout (KO) mice. The KO mice were highly susceptive to stress-induced mitochondrial remodelling and exhibited accelerated myopathy and cardiac dysfunction under stressed conditions. Furthermore, we demonstrate that the ms2 modifications of mt-tRNAs were sensitive to oxidative stress and were reduced in patients with mitochondrial disease. These findings highlight the fundamental role of ms2 modifications of mt-tRNAs in mitochondrial protein synthesis and their pathological consequences in mitochondrial disease.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Mtu1-mediated thiouridine formation of mitochondrial tRNAs is required for mitochondrial translation and is involved in reversible infantile liver injury2016
Author(s)
Wu, Y., Wei, F. Y., Kawarada, L., Suzuki, T., Araki, K., Komohara, Y., Fujimura, A., Kaitsuka, T., Takeya, M., Oike, Y., Suzuki, T., Tomizawa, K.
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Journal Title
PLoS genetics
Volume: 12
Issue: 9
Pages: e1006355-e1006355
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cdk5rap1-mediated 2-methylthio modification of mitochondrial tRNAs governs protein translation and contributes to myopathy in mice and humans.2015
Author(s)
Wei FY, Zhou B, Suzuki T, Miyata K, Ujihara Y, Horiguchi H, Takahashi N, Xie P, Michiue H, Fujimura A, Kaitsuka T, Matsui H, Koga Y, Mohri S, Suzuki T, Oike Y, Tomizawa K.
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Journal Title
Cell Metab
Volume: 21
Issue: 3
Pages: 413-6
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Possible role of cortactin phosphorylation by protein kinase Cα in actin-bundle formation at growth cone.2015
Author(s)
Yamada H, Kikuchi T, Masumoto T, Wei FY, Abe T, Takeda T, Nishiki T, Tomizawa K, Watanabe M, Matsui H, Takei K.
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Journal Title
Biology of the Cell
Volume: 107
Issue: 9
Pages: 319-330
DOI
Related Report
Peer Reviewed
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