1999 Fiscal Year Final Research Report Summary
Studies on the Biological Functions of Neuron-specific RNA-binding Proteins in Cultured Cells
| Project/Area Number |
09480187
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kobe University |
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Principal Investigator |
SAKAMOTO Hiroshi Kobe University, Faculty of Science, Professor, 理学部, 教授 (00187048)
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| Project Period (FY) |
1997 – 1999
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| Keywords | neuron / RNA-binding protein / Hu proteins / nuclear export signal / Subcellular localization / PC12 cell / P19 cell |
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| Research Abstract |
ELAV-like neuronal RNA-binding proteins are highly conserved in many neuron-containing organisms and have been implicated in neuronal development and differentiation. Mammalian neuron-specific ELAV-like Hu proteins (HuB, HuC and HuD) and Drosophila ELAV, but not HuR, were found to induce neurite outgrowth when overexpressed in rat PC12 cells. Functional analysis of HuD deletion mutants demonstrated the importance of two conserved RNA-binding domains (RBDs 1 and 3) and the indispensability of the linker region between RBDs 2 and 3 for the neurite-inducing activity. Further analyses suggested the importance of nucleocytoplasmic shuttling of HuD mediated by a novel nuclear export signal (NES) sequence in the linker region for the neurite-inducing activity. Moreover, two HuD deletion mutants containing the linker region dominantly inhibited the wild-type neurite-inducing activity, although they had no neurite-inducing activity per se, suggesting that saturable intracellular trafficking mediated by the linker region is required for the neurite induction by HuD. Interestingly, the same dominant negative mutants significantly inhibited retinoic acid-induced neuronal differentiation of mouse embryonal carcinoma P19 cells. Our results suggest the presence of a novel NES in neuron-specific Hu proteins and the importance of their cytoplasmic localization, through nucleocytoplasmic shuttling, for the initiation of neuronal differentiation.
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[Publications] Handa,N., Nureki,O., Kurimoto,K., Kim,I., Sakamoto,H., Shimura,Y., Muto,Y. and Yokoyama,S.: "Structural basis for tra mRNA precursor recognition by the Sex-lethal protein"Nature. 398. 579-585 (1999)
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[Publications] Chi,S-W., Muto,Y., Inoue,M., Kim,I., Sakamoto,H., Shimura,Y., Yokoyama,S., Choi,B-S. and Kim,H.: "Chemical shift perturbation studies of the interactions of the second RNA-binding domain of the Drosophila Sex-lethal protein with the transformer pre-mRNA polyuridine tract and 3' splicing-site sequences"Eur. J. Biochem.. 259. 1-13 (1999)
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