Elucidation of Ataxin-2-mediated neurodegeneration
| Project/Area Number |
25293201
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Osaka University |
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Principal Investigator |
Kawahara Yukio 大阪大学, 医学(系)研究科(研究院), 教授 (80542563)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 脳神経疾患 / RNA / 脊髄小脳変性症 / 筋萎縮性側索硬化症 / ALS / 神経変性疾患 / 遺伝子 / RNA結合タンパク質 / 痴呆 |
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| Outline of Final Research Achievements |
The gene encoding Ataxin-2 is mutated in the patients with some neurodegenerative diseases, such as spinocerebellar ataxia type 2 and amyotrophic lateral sclerosis. This finding suggests a common pathogenic role of Ataxin-2 in these neurodegenerative diseases. Therefore, a comprehensive understanding of the physiological functions of Ataxin-2 is the first step for elucidating the mechanism underlying Ataxin-2-mediated neurodegeneration. However, although Ataxin-2 has been implicated to be involved in RNA metabolism, the exact biological mechanism and in vivo targets remain unknown. In this study, we identified that Ataxin-2 associates with RNA-induced silencing complex that is required for microRNA-mediated gene silencing. Furthermore, we found that Ataxin-2 binds to distinct elements in the 3’UTRs of target mRNAs. The functional analyses revealed that Ataxin-2 stabilizes target mRNAs, which was attenuated by disease-associated mutations.
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Direct binding of Ataxin-2 to distinct elements in 3’UTRs promotes mRNA stability and protein expression.2014
Author(s)
Yokoshi, M., Li, Q., Yamamoto, M., Okada, H., Suzuki, Y., and Kawahara, Y.
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Journal Title
Molecular Cell
Volume: 55
Pages: 186-198
DOI
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Peer Reviewed / Acknowledgement Compliant
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[Presentation] Ataxin-2 stabilizes mRNA through the direct binding to the distinct motifs in 3’UTRs.2015
Author(s)
Yamamoto, M., Yokoshi, M., Li, Q., Okada, H., Suzuki, Y., Kawahara, Y
Organizer
NCI Symposium “RNA Biology 2015”
Place of Presentation
Bethesda, MA, USA
Year and Date
2015-03-11 – 2015-03-12
Related Report
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[Presentation] Ataxin-2 promotes the stability of mRNA through the direct binding to the distinct motifs.2014
Author(s)
Yokoshi, M., Li, Q., Yamamoto, M., Okada, H., Suzuki, Y., *Kawahara, Y
Organizer
Joint Australia and Japan RNA Meeting 2014
Place of Presentation
Sydney, Australia
Year and Date
2014-11-02 – 2014-11-05
Related Report
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[Presentation] Ataxin-2 promotes the stability of mRNA through the direct binding to the distinct motifs.2014
Author(s)
Yokoshi, M., Li, Q., Yamamoto, M., Okada, H., Suzuki, Y., Kawahara, Y
Organizer
EMBL Symposium “Complex Life of mRNA”
Place of Presentation
Heidelberg, Germany
Year and Date
2014-10-05 – 2014-10-08
Related Report
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[Presentation] Comprehensive analysis of the roles of TDP-43 and FUS in RNA processing2013
Author(s)
Li, Q., Yamamoto, M., Seno, S., Matsuda, H., Suzuki, Y., Kawahara Y.
Organizer
第36回日本神経科学大会
Place of Presentation
京都
Related Report
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