Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/30652
Title: Heterogeneous nuclear ribonucleoprotein U (HNRNPU) safeguards the developing mouse cortex.
Austin Authors: Sapir, Tamar;Kshirsagar, Aditya;Gorelik, Anna;Olender, Tsviya;Porat, Ziv;Scheffer, Ingrid E ;Goldstein, David B;Devinsky, Orrin;Reiner, Orly
Affiliation: The University of Melbourne, Royal Children's Hospital, and Murdoch Children's Research Institutes, Melbourne, VIC, Australia..
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel..
Austin Health
Flow Cytometry Unit, Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel..
Institute for Genomic Medicine, Columbia University, New York, NY, USA..
NYU Langone Medical Center, NYU, New York, NY, USA..
The Florey Institute of Neuroscience and Mental Health
Issue Date: 21-Jul-2022
Date: 2022
Publication information: Nature communications 2022; 13(1): 4209
Abstract: 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.
URI: https://ahro.austin.org.au/austinjspui/handle/1/30652
DOI: 10.1038/s41467-022-31752-z
ORCID: http://orcid.org/0000-0001-8926-9353
http://orcid.org/0000-0003-3059-181X
http://orcid.org/0000-0002-2311-2174
http://orcid.org/0000-0003-0044-4632
http://orcid.org/0000-0001-7560-9599
Journal: Nature communications
PubMed URL: 35864088
PubMed URL: https://pubmed.ncbi.nlm.nih.gov/35864088/
Type: Journal Article
Appears in Collections:Journal articles

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