Elucidation of a novel mechanism relevant to disruption of microRNA biogenesis, explaining neurodevelopmental diseases.
| Project/Area Number |
24240051
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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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| Research Field |
Neuroscience in general
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| Research Institution | Kyushu University (2013-2015)
Nara Institute of Science and Technology (2012) |
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Principal Investigator |
Nakashima Kinichi 九州大学, 医学(系)研究科(研究院), 教授 (80302892)
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| Co-Investigator(Renkei-kenkyūsha) |
TSUJIMURA Keita 九州大学, 大学院医学研究院, 特任助教 (60588474)
FUKAO Yoichiro 奈良先端科学技術大学院大学, バイオサイエンス研究科 (80432590)
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| Project Period (FY) |
2012-05-31 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥42,120,000 (Direct Cost: ¥32,400,000、Indirect Cost: ¥9,720,000)
Fiscal Year 2015: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2014: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2013: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2012: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
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| Keywords | 神経科学 / レット症候群 / MeCP2 / エピジェネティクス / マイクロRNA / miRNA / ニューロン |
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| Outline of Final Research Achievements |
Rett syndrome (RTT) is a neurodevelopmental disorder caused by MECP2 mutations. Although emerging evidence suggests that MeCP2 deficiency is associated with dysregulation of mechanistic target of rapamycin (mTOR), which functions as a hub for various signaling pathways, the mechanism underlying this association and the molecular pathophysiology of RTT remain elusive. We show here that MeCP2 promotes the posttranscriptional processing of particular microRNAs (miRNAs) as a component of the microprocessor Drosha complex. Among the MeCP2-regulated miRNAs, we found that miR-199a positively controls mTOR signaling by targeting inhibitors for mTOR signaling. miR-199a and its targets have opposite effect on mTOR activity, ameliorating and inducing RTT neuronal phenotypes, respectively. Furthermore, genetic deletion of miR-199a-2 led to a reduction of mTOR activity in the brain and recapitulated numerous RTT phenotypes in mice.
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Report
(5 results)
Research Products
(15 results)
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[Journal Article] miR-199a links MeCP2 with mTOR signaling and its dysregulation leads to Rett Syndrome phenotypes.2015
Author(s)
Tsujimura K, Irie K, Nakashima H, Egashira Y, Fukao Y, Fujiwara M, Itoh M, Uesaka M, Imamura T, Nakahata Y, Yamashita Y, Abe T, Takamori S, Nakashima K.
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Journal Title
Cell Reports
Volume: 12
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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