Mammalian ELAV-like neuronal RNA-binding proteins HuB and HuC promote neuronal development in both the central and the peripheral nervous systems

Wado Akamatsu, Hirotaka J. Okano, Noriko Osumi, Takayoshi Inoue, Shun Nakamura, Shinichi Sakakibara, Masayuki Miura, Nobutake Matsuo, Robert B. Darnell, Hideyuki Okano

Research output: Contribution to journalArticle

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Abstract

Hu proteins are mammalian embryonic lethal abnormal visual system (ELAV)-like neuronal RNA-binding proteins that contain three RNA recognition motifs. Although Drosophila ELAV is required for the correct differentiation and survival of neurons, the roles played by the Hu genes in the mammalian nervous system remain largely unknown. To explore the in vivo functions of mouse Hu proteins, we overexpressed them in rat pheochromocytoma PC12 cells, where they induced neuronal phenotype in the absence of nerve growth factor. We have characterized the functions of various forms of mHuB and mHuC bearing point mutations or deletions. Mutants of mHuC that had amino acid exchanges in the RNP1 domain of the first or second RNA recognition motifs (RRMs) lost biologic activity as well as RNA-binding activity. In addition, the mutants containing only the third RRM failed to induce the neuronal phenotype in PC12 cells and inhibited the biologic activity of cotransfected wild-type mHuB and mHuC, thus acting as a dominant-negative form. However, these mutants could not suppress the nerve growth factor-induced differentiation of PC12 cells. Further, we misexpressed wild-type and dominant-negative Hu in E9.5 mouse embryos, by using electroporation into the neural tube at the level of the rhombencephalon, mHuB and mHuC induced the ectopic expression of neuronal markers, whereas the dominant-negative forms of mHuB and mHuC suppressed the differentiation of central nervous system motor neurons. From these results, we suggest that Hu proteins are required for neuronal differentiation in the mammalian nervous system.

Original languageEnglish
Pages (from-to)9885-9890
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number17
DOIs
Publication statusPublished - 1999 Aug 17
Externally publishedYes

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RNA-Binding Proteins
PC12 Cells
Peripheral Nervous System
Central Nervous System
Nerve Growth Factor
Nervous System
Phenotype
Rhombencephalon
Neural Tube
Proteins
Electroporation
Pheochromocytoma
Motor Neurons
Point Mutation
Drosophila
Embryonic Structures
RNA
Neurons
Amino Acids
Genes

ASJC Scopus subject areas

  • Genetics
  • General

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Mammalian ELAV-like neuronal RNA-binding proteins HuB and HuC promote neuronal development in both the central and the peripheral nervous systems. / Akamatsu, Wado; Okano, Hirotaka J.; Osumi, Noriko; Inoue, Takayoshi; Nakamura, Shun; Sakakibara, Shinichi; Miura, Masayuki; Matsuo, Nobutake; Darnell, Robert B.; Okano, Hideyuki.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 17, 17.08.1999, p. 9885-9890.

Research output: Contribution to journalArticle

Akamatsu, Wado ; Okano, Hirotaka J. ; Osumi, Noriko ; Inoue, Takayoshi ; Nakamura, Shun ; Sakakibara, Shinichi ; Miura, Masayuki ; Matsuo, Nobutake ; Darnell, Robert B. ; Okano, Hideyuki. / Mammalian ELAV-like neuronal RNA-binding proteins HuB and HuC promote neuronal development in both the central and the peripheral nervous systems. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 17. pp. 9885-9890.
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AU - Akamatsu, Wado

AU - Okano, Hirotaka J.

AU - Osumi, Noriko

AU - Inoue, Takayoshi

AU - Nakamura, Shun

AU - Sakakibara, Shinichi

AU - Miura, Masayuki

AU - Matsuo, Nobutake

AU - Darnell, Robert B.

AU - Okano, Hideyuki

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