RRC ID 28656
Author Urano Y, Iiduka M, Sugiyama A, Akiyama H, Uzawa K, Matsumoto G, Kawasaki Y, Tashiro F.
Title Involvement of the mouse Prp19 gene in neuronal/astroglial cell fate decisions.
Journal J Biol Chem
Abstract 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 PRP19alpha 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 in-frame 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.
Volume 281(11)
Pages 7498-514
Published 2006-3-17
DOI 10.1074/jbc.M510881200
PII M510881200
PMID 16352598
MeSH Alternative Splicing Amino Acid Sequence Animals Base Sequence Blotting, Northern Carrier Proteins / physiology* Cell Differentiation Cell Line Cell Lineage Cells, Cultured Chromatin Immunoprecipitation Chromatography, Gel Cloning, Molecular Cyclophilin A / chemistry DNA Primers / chemistry DNA Repair Enzymes DNA, Complementary / metabolism Dose-Response Relationship, Drug Down-Regulation Genetic Vectors Green Fluorescent Proteins / metabolism Immunoprecipitation Luciferases / metabolism Mice Mice, Inbred ICR Models, Biological Molecular Sequence Data Neuroglia / metabolism* Neurons / metabolism Nuclear Proteins Oligonucleotides / chemistry Promoter Regions, Genetic Protein Binding Protein Structure, Tertiary RNA / chemistry RNA / metabolism RNA Splicing Factors RNA, Messenger / metabolism Rats Reverse Transcriptase Polymerase Chain Reaction Sequence Homology, Amino Acid Spliceosomes / metabolism Time Factors Tissue Distribution Two-Hybrid System Techniques
IF 4.238
Times Cited 25
DNA material pFlag-CMV2/PRP19beta (RDB07945)