Elucidation of the molecular mechanism of disease development by disruption of RNA metabolism
Project/Area Number |
16H05154
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pathological medical chemistry
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Research Institution | Oita University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
花田 礼子 大分大学, 医学部, 教授 (00343707)
|
Project Period (FY) |
2016-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
|
Keywords | RNA / 希少疾患 / 遺伝性神経変性疾患 / RNA代謝 / 動物疾患モデル / 橋小脳低形成 / 遺伝性疾患 / 神経変性疾患 / 疾患モデル動物 / 遺伝学 / 脳神経疾患 |
Outline of Final Research Achievements |
In this study, we investigated the molecular mechanism of neurodegeneration involving tRNA metabolism and the function of a novel RNA kinase molecule, NOL9. In vitro and in vivo analysis of various tRNA fragments, which have been reported to cause neuronal cell death, revealed that 5'Tyr-tRF derived from tyrosine tRNA induces p53-dependent neuronal cell death. In vitro kinase assays using the mouse fibroblasts or recombinant proteins produced by a cell-free protein expression system were performed for NOL9. However, no kinase activity was observed in NOL9 molecules, which was surprisingly different from previous reports.
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Academic Significance and Societal Importance of the Research Achievements |
本研究において、チロシンtRNAから生じるsmall RNAが神経細胞死を惹起し、神経変性疾患の原因になることを示した。また、このsmall RNAはPKM2を結合することでPKM2自体の機能やそれが関与するシグナル伝達機構に影響を及ぼす可能性がある。このように、新たな希少難治性疾患の分子病態メカニズムが明らかになったことで、治療創薬につながる可能性が示された。また、新たな神経細胞死の病態メカニズムが明らかになったことで、高齢社会で社会問題となっているパーキンソン病やアルツハイマー病に対する新たな治療につながる可能性がある。
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Report
(5 results)
Research Products
(41 results)
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[Journal Article] Cocaine has some effect on Neuromedin U expressing neurons related to the brain reward system.2020
Author(s)
Anan M, Higa R, Shikano K, Shide M, Soda A, Apolinario MEC, Mori K, Shin T, Miyazato M, Mimata H, Hikida T, Hanada T, Nakao K, Kangawa K, Hanada R
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Journal Title
Related Report
Peer Reviewed / Open Access
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[Journal Article] CLP1 acts as the main RNA kinase in mice2020
Author(s)
Fujinami H, Shiraishi H, Hada K, Inoue M, Morisaki I, Higa R, Shin T, Kobayashi T, Hanada R, Penninger JM, Mimata H, Hanada T.
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Journal Title
Biochem Biophys Res Commun.
Volume: 525
Issue: 1
Pages: 129-134
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] AIF-regulated oxidative phosphorylation supports lung cancer development2019
Author(s)
Rao S, Mondragon L, Pranjic B, Hanada T, Stoll G, Sica V,Modjtahedi N, Pai TP, Onji M, Uribesalgo I, Hanada R, Koglgruber R, Cronin SJ, Kroemer G, Penninger JM et al.
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Journal Title
Cell Res. 2019 Jul;29(7):579-591. doi: 10.1038/s41422-019-0181-4. Epub 2019 May 27.
Volume: 29
Issue: 7
Pages: 579-591
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] CD105 maintains the thermogenic program of beige adipocytes by regulating Smad2 signaling2018
Author(s)
Higa R, Hanada T, Teranishi H, Miki D, Seo K, Hada K, Shiraishi H, Mimata H, Hanada R, Kangawa K, Murai T, Nakao K.
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Journal Title
Molecular and Cellular Endocrinology
Volume: 印刷中
Pages: 184-193
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The tumor suppressor Hace1 is a critical regulator of TNFR1-mediated cell fate.2016
Author(s)
Tortola L, Nitsch R, Bertrand MJ, Kogler M, Redouane Y, Kozieradzki I, Uribesalgo I, Fennell LM, Daugaard M, Klug H, Wirnsberger G, Wimmer R, Perlot T, Sarao R, Rao S, Hanada T, Takahashi N, Kernbauer E, Demiroz D, Superti-Furga G, Decker T, Pichler A, Ikeda F, Kroemer G, Vandenabeele P, Sorensen PH, Penninger JM
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Journal Title
Cell reports
Volume: 15
Pages: 1481-1492
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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