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1999 Fiscal Year Final Research Report Summary

Studies on the Biological Functions of Neuron-specific RNA-binding Proteins in Cultured Cells

Research Project

Project/Area Number 09480187
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionKobe University

Principal Investigator

SAKAMOTO Hiroshi  Kobe University, Faculty of Science, Professor, 理学部, 教授 (00187048)

Project Period (FY) 1997 – 1999
Keywordsneuron / RNA-binding protein / Hu proteins / nuclear export signal / Subcellular localization / PC12 cell / P19 cell
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.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Kasashima, K.: "Cytoplasmic localization is required for the mammalian ELV-like protein HuD to induce neuronal differentiation"Genes Cells. 4. 667-683 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujita, M.: "Neuronal expression of a Caenorhabditis elegans elav-like gene and the effect of its ectopic expression"Biochem. Biophys. Res. Commun.. 260. 646-652 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Handa, N.: "Structural basis for tra mRNA precursor recognition by the Sex-lethal protein"Nature. 398. 579-585 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chi, S.W.: "Chemical shift perturbation studies of the interactions of the second RNA-binding domain of the Drosophila Sex-lethal protein with the tra pre-mRNA polyuridinetract"Euro. J. Biochem.. 259. 1-13 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujita, M: "Expression of spliceosome-associated protein 49 is required for early embryogenesis in C. elegans"Biochem. Biophys. Res. Commun.. 253. 80-84 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka, Y.: "Polycistronic expression and RNA-binding specificity f the C. elegans homologue of the spliceosome-associated protein SAP49"J. Biochem.. 121. 739-745 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kasashima,K., Terashima,K., Yamamoto,K., Sakashita,E. and Sakamoto,H.: "Cytoplasmic localization is required for the mammalian ELAV-like protein HuD to induce neuronal differentiation"Genes Cells. 4. 667-683 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujita,M., Kawano,T., Ohta,A. and Sakamoto,H.: "Neuronal expression of a Caenorhabditis elegans elav-like gene and the effect of its ectopic expression"Biochem. Biophys. Res. Commun.. 260. 646-652 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujita,M., Kawano,T., Terashima,K., Tanaka,Y. and Sakamoto,H.: "Expression of spliceosome-associated protein 49 is required for early embryogenesis in C. elegans"Biochem. Biophys. Res. Commun.. 253. 80-84 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka,Y., Ohta,A., Terashima,K. and Sakamoto,H.: "Polycistronic expression and RNA-binding specificity of the C.elegans homologue of the spliceosome-associated protein SAP49"J. Biochem.. 121. 739-745 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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