An asymmetrically localized Staufen2-dependent RNA complex regulates maintenance of mammalian neural stem cells.
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.
Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada M5G 1L7.
John P
JP
Vessey
Gianluca
G
Amadei
Sarah E
SE
Burns
Michael A
MA
Kiebler
David R
DR
Kaplan
Freda D
FD
Miller
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology*; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; C471243:PUM2 protein, human; D016601:RNA-Binding Proteins; C471845:stau2 protein, mouse; C541494:DDX1 protein, mouse; D053487:DEAD-box RNA Helicases