title: Context-dependent regulation of Musashi-mediated mRNA translation and cell cycle regulation.
abstract: Musashi-mediated mRNA translational control has been implicated in the promotion of physiological and pathological stem cell proliferation. During self-renewal of mammalian stem cells, Musashi has been proposed to act to repress the translation of mRNAs encoding inhibitors of cell cycle progression. By contrast, in maturing Xenopus oocytes Musashi activates translation of target mRNAs that encode proteins promoting cell cycle progression. The mechanisms directing Musashi to differentially control mRNA translation in mammalian stem cells and Xenopus oocytes is unknown. In this study, we demonstrate that the mechanisms defining Musashi function lie within the cellular context. Specifically, we show that murine Musashi acts as an activator of translation in maturing Xenopus oocytes while Xenopus Musashi functions as a repressor of target mRNA translation in mammalian cells. We further demonstrate that within the context of a primary mammalian neural stem/progenitor cell, Musashi can be converted from a repressor of mRNA translation to an activator of translation in response to extracellular stimuli. We present current models of Musashi-mediated mRNA translational control and discuss possible mechanisms for regulating Musashi function. An understanding of these mechanisms presents exciting possibilities for development of therapeutic targets to control physiological and pathological stem cell proliferation.
authors.affiliation: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: MacNicol
authors.forename: Chad E
authors.initials: CE
authors.lastname: Cragle
authors.forename: Angus M
authors.initials: AM
authors.lastname: MacNicol
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D002478:Cells, Cultured; D006801:Humans; D009419:Nerve Tissue Proteins / Q000502:physiology*; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*; D014981:Xenopus
chemical_list: C104786:Msi1h protein, mouse; C499059:Msi2h protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins