6533b829fe1ef96bd128ae92
RESEARCH PRODUCT
Nucleocytoplasmic transport of the RNA-binding protein CELF2 regulates neural stem cell fates.
Julia BaptistaOlaf BodamerDrayden KoppDrayden KoppLara MenziesAntonio VitobelloGuiqiong HeShreeya KediaShreeya KediaLouise Amlie-wolfWilliam J. BruckerLaurence FaivreFrédéric Tran Mau-themAlison MalePengqiang WenPengqiang WenA. Micheil InnesA. Micheil InnesGuang YangGuang YangQuan LongQuan LongNina B. GoldQuentin ThomasMikko MuonaSarah L. EricksonSarah L. EricksonKaren W. GrippMelissa J. MacphersonMelissa J. MacphersonMelissa J. MacphersonMohamad-reza AghanooriMohamad-reza AghanooriKatie GueganKaylan M.l. BurnsKaylan M.l. BurnsXing-chang Weisubject
0301 basic medicineRegulation of gene expressionNeurogenesisRNA-Binding ProteinsTranslation (biology)RNA-binding proteinCell DifferentiationNerve Tissue ProteinsBiologyCell fate determinationGeneral Biochemistry Genetics and Molecular BiologyNeural stem cellCell biology03 medical and health sciences030104 developmental biology0302 clinical medicineNeural Stem CellsNucleocytoplasmic TransportCELF ProteinsHumansProgenitor cell030217 neurology & neurosurgerydescription
The development of the cerebral cortex requires balanced expansion and differentiation of neural stem/progenitor cells (NPCs), which rely on precise regulation of gene expression. Because NPCs often exhibit transcriptional priming of cell-fate-determination genes, the ultimate output of these genes for fate decisions must be carefully controlled in a timely fashion at the post-transcriptional level, but how that is achieved is poorly understood. Here, we report that de novo missense variants in an RNA-binding protein CELF2 cause human cortical malformations and perturb NPC fate decisions in mice by disrupting CELF2 nucleocytoplasmic transport. In self-renewing NPCs, CELF2 resides in the cytoplasm, where it represses mRNAs encoding cell fate regulators and neurodevelopmental disorder-related factors. The translocation of CELF2 into the nucleus releases mRNA for translation and thereby triggers NPC differentiation. Our results reveal that CELF2 translocation between subcellular compartments orchestrates mRNA at the translational level to instruct cell fates in cortical development.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-11-16 | Cell reports |