Inhibition of neurogenesis by SRp38, a neuroD-regulated RNA-binding protein.
Although serine-arginine rich (SR) proteins have often been implicated in the positive regulation of splicing, recent studies have shown that one unusual SR protein, SRp38, serves, contrastingly, as a splicing repressor during mitosis and stress response. We have identified a novel developmental role for SRp38 in the regulation of neural differentiation. SRp38 is expressed in the neural plate during embryogenesis and is transcriptionally induced by the neurogenic bHLH protein neuroD. Overexpression of SRp38 inhibits primary neuronal differentiation at a step between neurogenin and neuroD activity. This repression of neuronal differentiation requires activation of the Notch pathway. Conversely, depletion of SRp38 activity results in a dysregulation of neurogenesis. Finally, SRp38 can interact with the peptidyltransferase center of 28S rRNA, suggesting that SRp38 activity may act, in part, via regulation of ribosome biogenesis or function. Strikingly, recent studies of several cell cycle regulators during primary neurogenesis have also revealed a crucial control step between neurogenin and neuroD. SRp38 may mediate one component of this control by maintaining splicing and translational silencing in undifferentiated neural cells.
Liu
Karen J
KJ
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Harland
Richard M
RM
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D036703:Blastula / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051880:Receptors, Notch; D015398:Signal Transduction / Q000502:physiology; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis
D051792:Basic Helix-Loop-Helix Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D016601:RNA-Binding Proteins; D051880:Receptors, Notch; D029867:Xenopus Proteins; C500590:SRSF10 protein, Xenopus; C101907:neurogenin, Xenopus; C093564:Neurogenic differentiation factor 1