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

ABSTRACT: 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-1

SUBMITTER: Tajima Y 

PROVIDER: S-EPMC10382602 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature