| Project/Area Number |
23500431
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Survival Motor Neuron / 脊髄性筋萎縮症 / hnRNP A2 / RNA結合タンパク質 / Translational control / Motor Neuron Disease / SMN / 翻訳制御 / 軸索輸送 / キネシン / SMA / ALS / モーターニューロン病 / RNA binding protein / translatinal control / Spinal Muscular Atrophy / axonal transport / kinesin / ＡＬＳ / hnRNP A1 / translational control / Transcription |
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| Research Abstract |
Survival Motor Neuron (SMN) protein is involved in snRNPs assembly, essential components in splicing. A lack of SMN due to homologous loss of SMN1 gene results hereditary neurodegenerative disease, Spinal Muscular Atrophy (SMA). Previously we found that the specific suppression of hnRNP A2 by RNAi treatment induced a reduction of SMN production in SMA patient fibroblast cell. We have analyzed the molecular detail of this regulation. We provided evidences that hnRNP A2 specifically binds A2 binding sequence at 3-UTR of SMN mRNA, and increases the interaction of mRNAs and polyribosome to enhance translation efficiency. Our data suggests that hnRNP A2 is essential for the effective translation of SMN1/2 mRNA, and that this A2 binding site functions as a translation enhancer. Our findings not only define the new regulatory mechanism to control SMN translation by hnRNP A2 specifically, but also implicate the new therapeutic drug development for treatment of SMA.
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