MOUSE-MUSASHI-1, A NEURAL RNA-BINDING PROTEIN HIGHLY ENRICHED IN THE MAMMALIAN CNS STEM-CELL

There is increasing interest in the role of RNA-binding proteins durin g neural development. Drosophila Musashi is one of the neural RNA-bind ing proteins essential for neural development and required for asymmet ric cell divisions in the Drosophila adult sensory organ development. Here, a novel mammalian neural RNA-binding protein, mouse-Musashi-1, w as identified based on the homology to Drosophila Musashi and Xenopus NRP-1. In the developing CNS, mouse-Musashi-1 protein was highly enric hed in the CNS stem cell. Single-cell culture experiments indicated th at mouse-Musashi-1 expression is associated with neural precursor cell s that are capable of generating neurons and glia. In contrast, in ful ly differentiated neuronal and glial cells mouse-Musashi-1 expression is lost. This expression pattern of mouse-Musashi-1 is complementary t o that of another mammalian neural RNA-binding protein, Hu (a mammalia n homologue of a Drosophila neuronal RNA-binding protein Elav), that i s expressed in postmitotic neurons within the CNS. In vitro studies in dicated that mouse-Musashi-1 possesses binding preferences on poly(G) RNA homopolymer, whereas Hu is known to preferentially bind to short A /U-rich regions in RNA. Based on their differential expression pattern s and distinct preferential target RNA sequences, we believe that the mouse-Musashi-1 and Hu proteins may play distinct roles in neurogenesi s, either through sequential regulatory mechanisms or differential sor ting of mRNA populations during asymmetric division of neural precurso r cells. (C) 1996 Academic Press, Inc.