Nucleocytoplasmic transport of the RNA-binding protein CELF2 regulates neural stem cell fates
dc.contributor.author | MacPherson, MJ | |
dc.contributor.author | Erickson, SL | |
dc.contributor.author | Kopp, D | |
dc.contributor.author | Wen, P | |
dc.contributor.author | Aghanoori, M-R | |
dc.contributor.author | Kedia, S | |
dc.contributor.author | Burns, KML | |
dc.contributor.author | Vitobello, A | |
dc.contributor.author | Tran Mau-Them, F | |
dc.contributor.author | Thomas, Q | |
dc.contributor.author | Gold, NB | |
dc.contributor.author | Brucker, W | |
dc.contributor.author | Amlie-Wolf, L | |
dc.contributor.author | Gripp, KW | |
dc.contributor.author | Bodamer, O | |
dc.contributor.author | Faivre, L | |
dc.contributor.author | Muona, M | |
dc.contributor.author | Menzies, L | |
dc.contributor.author | Baptista, Julia | |
dc.contributor.author | Guegan, K | |
dc.contributor.author | Male, A | |
dc.contributor.author | Wei, X-C | |
dc.contributor.author | He, G | |
dc.contributor.author | Long, Q | |
dc.contributor.author | Innes, AM | |
dc.contributor.author | Yang, G | |
dc.date.accessioned | 2022-05-03T17:56:09Z | |
dc.date.issued | 2021-06 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.other | 109226 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/19162 | |
dc.description.abstract |
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. | |
dc.format.extent | 109226-109226 | |
dc.format.medium | ||
dc.language | en | |
dc.language.iso | eng | |
dc.publisher | Elsevier BV | |
dc.subject | CELF2 | |
dc.subject | RNA-binding proteins | |
dc.subject | cell fate decision | |
dc.subject | cortical development | |
dc.subject | neural stem cells | |
dc.subject | neurodevelopmental disorder | |
dc.subject | neurogenesis | |
dc.subject | nucleocytoplasmic translocation | |
dc.subject | rare disease | |
dc.subject | translational repression | |
dc.subject | CELF Proteins | |
dc.subject | Cell Differentiation | |
dc.subject | Humans | |
dc.subject | Nerve Tissue Proteins | |
dc.subject | Neural Stem Cells | |
dc.subject | RNA-Binding Proteins | |
dc.title | Nucleocytoplasmic transport of the RNA-binding protein CELF2 regulates neural stem cell fates | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000659894300017&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 10 | |
plymouth.volume | 35 | |
plymouth.publication-status | Published | |
plymouth.journal | Cell Reports | |
dc.identifier.doi | 10.1016/j.celrep.2021.109226 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/Peninsula Medical School | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
dc.publisher.place | United States | |
dcterms.dateAccepted | 2021-05-13 | |
dc.rights.embargodate | 9999-12-31 | |
dc.identifier.eissn | 2211-1247 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1016/j.celrep.2021.109226 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2021-06-08 | |
rioxxterms.type | Journal Article/Review |