An Asymmetrically Localized Staufen2-Dependent RNA Complex Regulates Maintenance of Mammalian Neural Stem Cells

• Published in: Cell stem cell 2012-10, Vol.11 (4), p.517-528
• Main Authors: Vessey, John P., Amadei, Gianluca, Burns, Sarah E., Kiebler, Michael A., Kaplan, David R., Miller, Freda D.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Differentiation - genetics; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cell Survival - genetics; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; Fundamental and applied biological sciences. Psychology; HEK293 Cells; Humans; Mice; Molecular and cellular biology; Multiprotein Complexes - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neural Stem Cells - physiology; Neuroglia - physiology; Protein Transport; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2012.06.010

The cellular mechanisms that regulate self-renewal versus differentiation of mammalian somatic tissue stem cells are still largely unknown. Here, we asked whether an RNA complex regulates this process in mammalian neural stem cells. We show that the RNA-binding protein Staufen2 (Stau2) is apically localized in radial glial precursors of the embryonic cortex, where it forms a complex with other RNA granule proteins including Pumilio2 (Pum2) and DDX1, and the mRNAs for β-actin and mammalian prospero, prox1. Perturbation of this complex by functional knockdown of Stau2, Pum2, or DDX1 causes premature differentiation of radial glial precursors into neurons and mislocalization and misexpression of prox1 mRNA. Thus, a Stau2- and Pum2-dependent RNA complex directly regulates localization and, potentially, expression of target mRNAs like prox1 in mammalian neural stem cells, and in so doing regulates the balance of stem cell maintenance versus differentiation. ► A Stau2-RNA granule is asymmetrically localized in developing neural stem cells ► Disruption of this granule enhances neurogenesis and depletes stem cells ► prox1 mRNA associates with the Stau2 granule, and is also asymmetrically localized ► Stau2 maintains stem cells by localizing and potentially repressing target mRNAs Stem cells divide asymmetrically to expand differentiating progeny while maintaining the stem cell pool. This paper shows that an RNA granule containing Stau2 regulates balance of stem cell maintenance versus differentiation in radial glial precursors during cortical development.