The molecular mechanisms involved in neuronal/astroglial cell fate decisions during the development of mammalian central nervous system are poorly understood. Here we report that precursor RNA processing 19b, a splicing variant of mouse precursor RNA processing 19a corresponding to yeast precursor RNA processing 19 protein, could function as a neuron-astroglial switch during retinoic acid-primed neural differentiation of P19 cells. The b-variant possesses additional 19 amino acid residues in the N-terminal region of the a-variant in frame. Forced expression of the a-variant RNA caused the downregulation of oct-3/4 and nanog mRNA expressions during 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 cultivated in aggregated form without retinoic acid. In contrast, forced expression of the b-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 b-variant. Luciferase reporter assay mediated by oct-3/4 promoter revealed that cyclophilin A could act as a transcriptional activator and its activity was suppressed by the b-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 a-variant gene plays a pivotal role in neural differentiation and the b-variant participates in neuronal/astroglial cell fate decisions.