| Project/Area Number |
16207011
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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 |
Molecular biology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
SIOMI Mikiko The University of Tokushima, Institute for Genome Research, Associate Professor, ゲノム機能研究センター, 助教授 (20322745)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥45,890,000 (Direct Cost: ¥35,300,000、Indirect Cost: ¥10,590,000)
Fiscal Year 2006: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2005: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2004: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
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| Keywords | RNAi / Argonaute / small RNA / RNA silencing / rasiRNA / germline / Drosophila / FMR1 / Slicer / 精神遅滞 / RNA / 翻訳抑制 / P-body / microRNAs / 脆弱X症候群 / 遺伝性精神遅滞 / 機能性RNA / 翻訳制御 / miRNA / Dicer |
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| Research Abstract |
Fragile X syndrome is the most common cause of inherited mental retardation. Since after the discovery of the responsible gene, fmr1, for Fragile X, we have been trying to understand molecular mechanisms underlying fmrl gene function. Through the study, we found that fly genome contains a single gene highly similar to human fmr1, dfmr1, and that the protein product of dfmrl, dFMR1, is able to associate with one of RNAi factors, Argonaute (AGO). To elucidate the function of dFMR1 (eventually human FMR1), we thought that it is necessary to elucidate the molecular mechanisms underlying RNAi and its related pathways, and identify protein factors necessary for the processes. Results we obtained for the three years supported by KIBAN(A) are summarized below ;
We found that AGO1 and AGO2 bind specifically with miRNA and siRNA, respectively, and function as Slicer in gene silencing mechanisms in Drosophila. We also showed that ATP is not required for RNAi reaction in vitro. It was also shown that AGO2 functions as siRNA duplex unwinder in RNAi (Miyoshi et al. Genes Dev 2005). Lately, we studied members of the Argonautes exclusively expressed in germline cells (AGO3, Aub, and Piwi) and found that they function in silencing selfish genes such as retrotransposons through associating with rasiRNAs originated from transcripts of retrotransposons in germlines (Saito et al. 2006, Gunawardane et al. 2007). We also proposed a 'rasiRNA biogenesis' model through our study (Gunawardane et al. 2007).
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