NOVA1 acts on Impact to regulate hypothalamic function and translation in inhibitory neurons.

Autor:	Tajima Y; Laboratory of Molecular Neuro-oncology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA., Ito K; Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA., Yuan Y; Laboratory of Molecular Neuro-oncology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA., Frank MO; Laboratory of Molecular Neuro-oncology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA., Saito Y; Laboratory of Molecular Neuro-oncology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA., Darnell RB; Laboratory of Molecular Neuro-oncology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA; Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. Electronic address: darnelr@rockefeller.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Feb 28; Vol. 42 (2), pp. 112050. Date of Electronic Publication: 2023 Jan 29.
DOI:	10.1016/j.celrep.2023.112050
Abstrakt:	We describe a patient haploinsufficient for the neuronal RNA binding protein NOVA1 who developed a behavioral motor hyperactivity disorder, suggesting a role of NOVA1 in postnatal motor inhibition. To investigate Nova1's action in adult Gad2 + inhibitory neurons, we generated a conditional Nova1-null mouse (Nova1-cKO Gad2-cre ). Strikingly, the phenotypes of these mice show many similarities to the NOVA1 haploinsufficient patient and identify a function of Nova1 in the hypothalamus. Molecularly, Nova1 loss in Gad2-positive neurons alters downstream expression of Impact mRNA, along with a subset of RNAs encoding electron transport chain-related factors and ribosomal proteins. NOVA1 stabilizes Impact mRNA by binding its 3' UTR, antagonizing the actions of miR-138 and miR-124. Together, these studies demonstrate actions of NOVA1 in adult hypothalamic neurons, mechanisms by which it functions in translation and metabolism, including through direct binding to Impact mRNA, and illuminate its role in human neurologic disease. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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