| Project/Area Number |
14035243
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | The University of Tokushima |
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Principal Investigator |
SIOMI Haruhiko The University of Tokushima, Institute for Genome Research, Professor (60202107)
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| Co-Investigator(Kenkyū-buntansha) |
OKANO Hideyuki Keio University School of Medicine, 医学部, Professor (60160694)
C.SIOMI Mikiko Institute for Genome Research University of Tokushima, ゲノム機能研究センター, Associate Professor (20322745)
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| Project Period (FY) |
2002 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥123,400,000 (Direct Cost: ¥123,400,000)
Fiscal Year 2006: ¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 2005: ¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 2004: ¥25,100,000 (Direct Cost: ¥25,100,000)
Fiscal Year 2003: ¥25,100,000 (Direct Cost: ¥25,100,000)
Fiscal Year 2002: ¥25,200,000 (Direct Cost: ¥25,200,000)
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| Keywords | RNA-binding proteins / RNAi / fragile X syndrome / neuronal stem cells / FMR1 / Musashi / 脆弱X症候群 / 翻訳調節 / RNA結合タンパク質 / AGO2 / siRNA / 翻訳抑制 / ショウジョウバエ / 神経機能 / 神経幹細胞 / 遺伝子発現制御 / miRNA / 神経系前駆細胞 / musashi / 概日リズム / Notch-シグナル |
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| Research Abstract |
Work in the project was directed at understanding molecular mechanisms of how gene expression was regulated by RNA-binding proteins at posttranscriptional levels and how the lack of (or mutations in) specific RNA-binding proteins lead to human disease.
As model proteins, we mainly studied two RNA-binding proteins, FMRP and Musashi. FMRP is the product of the fragile X gene, mutations in which cause fragile X syndrome, the most common cause of hereditary mental retardation. We found that a Drosophila homolog of FMRP (dFMR1) forms a complex with AGO2, an essential component of RNAi in Drosophila. The association of dFMR1 with components of RNAi has the implication that defects in an RNAi-related process may cause human disease.
Recent findings demonstrate that translational regulation contributes to cell-fate specification. We found that the evolutionarily conserved, neural RNA-binding protein Musashi, controls neural cell fate. Further we showed that the protein functions in maintenance of the stem-cell state, differentiation, and tumorigenesis by repressing translation of particular mRNAs. We also found that in mammals it might play an important role in activating Notch signalling by repressing translation of the Notch inhibitor m-Numb.
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