2005 Fiscal Year Final Research Report Summary
The Role of RNA Binding Protein Hu in Neuronal Differentiation
| Project/Area Number |
16500206
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Keio University |
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Principal Investigator |
OKANO Hirotaka, James Keio University, School of Medicine, Department of Physiology, Associate Professor, 医学部, 助教授 (90338020)
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| Co-Investigator(Kenkyū-buntansha) |
OKANO Hideyuki Keio University, School of Medicine, Department of Physiology, Professor, 医学部, 教授 (60160694)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Hu / RNA binding protein / paraneoplastic neurologic disorders / translational control / neuronal differentiation / hnRNP K / neural stem cell |
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| Research Abstract |
Neuronal Hu RNA binding proteins are expressed immediately after the neuronal progenitor withdraw from cell cycle and continues to be expressed in postmitotic neurons. Recent studies indicate that overexpression of Hu is sufficient to induce neuronal differentiation by binding to UTR region of several target mRNAs in mammalian nervous system. To reveal molecular mechanism underlining timing-control of neuronal differentiation through. posttranscriptional regulation by Hu, we identified Hu associating proteins. We isolated RNP complexes associated with Hu from extracts of Hu-adenovirus infected culture cells and three proteins were identified by MALDI-TOF Mass. We revealed that hnRNPK, an RNA binding protein which is one of Hu associating proteins, bound to p21 mRNA 3'UTR, known as a target gene of Hu in vitro and in vivo, and repressed its translation in both nonneuronal and neuronal cells. Recently, it was reported that p21 not only inhibits the cell cycle but also contributes as a developmental regulator that induces axons and dendrites in newborn neurons. Then we speculated that the neuronal differentiation was regulated by two RNA binding proteins, Hu and hnRNPK through post-transcriptional regulation of p21 mRNA. By reporter assay, we found that p21 expression is controlled posttranscriptionally during neuronal differentiation and this regulation was dependent on its 3'UTR. Furthermore we showed that Hu induced neurite-outgrowth, stopped the cell cycle and upregulated p21 protein production in the mouse neuroblastoma N1E-115 cells. These effects were partially inhibited by hnRNPK. Taken all together, these data would suggest that Hu and hnRNPK controlled the timing of neuronal differentiation by regulating downstream genes.
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[Journal Article] RNA-binding protein HuD regulates neuronal cell identity and maturation2005
Author(s)
Akamatsu W, Fujihara H, Mitsuhashi T, Yano M, Shibata S, Hayakawa Y, Okano HJ, Sakakibara S, Takano H, Takano T, Takahashi T, Noda T, Okano H.
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Journal Title
Proc Natl Acad Sci USA. 102
Pages: 4625-4630
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Nedd9 protein, a Cas-L homologue, is upregulated after transient global ischemia in Rats.2005
Author(s)
Sasaki T, Iwata S, Okano HJ, Urasaki Y, Hamada J, Tanaka H, Dang NH, Okano H, Morimoto C.
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Journal Title
Stroke. 36
Pages: 2457-2462
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] In vivo imaging of engrafted neural stem cells : its application in evaluating the optimal timing of transplantation for spinal cord injury.2005
Author(s)
Okada S, Ishii K, Yamane J, Iwanami A, Ikegami T, Kato H, Iwamoto Y, Nakamura M, Miyoshi H, Okano HJ, Contag CH, Toyama Y, Okano H.
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Journal Title
FASEB J. 19
Pages: 1839-1841
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A novel marker for Purkinje cells, KIAA0864 protein. An analysis based on a monoclonal antibody HFB-16 in developing human cerebellum.2005
Author(s)
Nakamura Y, Yamamoto M, Oda E, Kanemura Y, Kodama E, Yamamoto A, Yamamoto H, Miyado K, Okano HJ, Fukagawa R, Higaki K, Yamasaki M, Okano H
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Journal Title
J Histochem Cytochem. 53
Pages: 423-430
Description
「研究成果報告書概要(欧文)」より
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