Heterogeneous nuclear ribonucleoprotein U (HNRNPU) safeguards the developing mouse cortex.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 07 2022
21 07 2022
Historique:
received:
30
07
2021
accepted:
30
06
2022
entrez:
21
7
2022
pubmed:
22
7
2022
medline:
26
7
2022
Statut:
epublish
Résumé
HNRNPU encodes the heterogeneous nuclear ribonucleoprotein U, which participates in RNA splicing and chromatin organization. Microdeletions in the 1q44 locus encompassing HNRNPU and other genes and point mutations in HNRNPU cause brain disorders, including early-onset seizures and severe intellectual disability. We aimed to understand HNRNPU's roles in the developing brain. Our work revealed that HNRNPU loss of function leads to rapid cell death of both postmitotic neurons and neural progenitors, with an apparent higher sensitivity of the latter. Further, expression and alternative splicing of multiple genes involved in cell survival, cell motility, and synapse formation are affected following Hnrnpu's conditional truncation. Finally, we identified pharmaceutical and genetic agents that can partially reverse the loss of cortical structures in Hnrnpu mutated embryonic brains, ameliorate radial neuronal migration defects and rescue cultured neural progenitors' cell death.
Identifiants
pubmed: 35864088
doi: 10.1038/s41467-022-31752-z
pii: 10.1038/s41467-022-31752-z
pmc: PMC9304408
doi:
Substances chimiques
Heterogeneous-Nuclear Ribonucleoprotein U
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4209Subventions
Organisme : CIHR
ID : 2397/18
Pays : Canada
Informations de copyright
© 2022. The Author(s).
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