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Originally published In Press as doi:10.1074/jbc.M510881200 on December 13, 2005

J. Biol. Chem., Vol. 281, Issue 11, 7498-7514, March 17, 2006
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Involvement of the Mouse Prp19 Gene in Neuronal/Astroglial Cell Fate Decisions*

Yumiko Urano, Masayuki Iiduka, Akinori Sugiyama, Hirotada Akiyama, Kouji Uzawa, Gaku Matsumoto, Yasushi Kawasaki, and Fumio Tashiro1

From the Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Yamazaki, Noda-shi, Chiba 270-8510, Japan

The molecular mechanisms involved in neuronal/astroglial cell fate decisions during the development of the mammalian central nervous system are poorly understood. Here, we report that PRP19beta, a splice variant of mouse PRP19{alpha} corresponding to the yeast PRP19 protein, can function as a neuron-astroglial switch during the retinoic acid-primed neural differentiation of P19 cells. The beta-variant possesses an additional 19 amino acid residues inframe in the N-terminal region of the {alpha}-variant. The forced expression of the {alpha}-variant RNA caused the down-regulation of oct-3/4 and nanog mRNA expression during the 12-48 h of the late-early stages of neural differentiation and was sufficient to convert P19 cells into neurons (but not glial cells) when the cells were cultured in aggregated form without retinoic acid. In contrast, the forced expression of the beta-variant RNA suppressed neuronal differentiation and conversely stimulated astroglial cell differentiation in retinoic acid-primed P19 cells. Based on yeast two-hybrid screening, cyclophilin A was identified as a specific binding partner of the beta-variant. Luciferase reporter assay mediated by the oct-3/4 promoter revealed that cyclophilin A could act as a transcriptional activator and that its activity was suppressed by the beta-variant, suggesting that cyclophilin A takes part in the induction of oct-3/4 gene expression, which might lead to neuroectodermal otx2 expression within 12 h of the immediate-early stages of retinoic acid-primed neural differentiation. These results show that the {alpha}-variant gene plays a pivotal role in neural differentiation and that the beta-variant participates in neuronal/astroglial cell fate decisions.


Received for publication, October 5, 2005 , and in revised form, December 12, 2005.

The nucleotide sequence(s) reported in this paper has been submitted to the DDBJ/Gen-BankTM/EBI Data Bank with accession number(s) AB020022 [GenBank] and AB222602 [GenBank] .

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed. Tel.: 81-4-7124-1501; Fax: 81-4-7125-1841; E-mail: ftashir{at}rs.noda.tus.ac.jp.


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