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Heterogeneous nuclear ribonucleoprotein U (HNRNPU) safeguards the developing mouse cortex
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Journal Article
Heterogeneous nuclear ribonucleoprotein U (HNRNPU) safeguards the developing mouse cortex
2022
Overview
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.
HNRNPU is an RNA splicing protein associated with brain disorders such as early onset seizures. Here they show that HNRNPU functions to maintain neural progenitors and their progeny by regulating splicing of key neuronal genes.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/1
/ 13/106
/ 14
/ 14/19
/ 14/34
/ 14/63
/ 38
/ 38/1
/ 38/39
/ Age
/ Animals
/ Brain
/ Embryos
/ Genes
/ Heterogeneous-Nuclear Ribonucleoprotein U - genetics
/ Humanities and Social Sciences
/ Intellectual Disability - genetics
/ Mice
/ Mutation
/ Progeny
/ RNA
/ Science
/ Seizures
/ Splicing
/ Synapses
