Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets

Agostini, M, Tucci, P, Killick, R, Candi, E and Sayan, BS ORCID: 2011, 'Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets' , Proceedings of the National Academy of Sciences, 108 (52) .

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The p53-family member TAp73 is a transcription factor that plays a key role in many biological processes. Here, we show that p73 drives the expression of microRNA (miR)-34a, but not miR-34b and -c, by acting on specific binding sites on the miR-34a promoter. Expression of miR-34a is modulated in parallel with that of TAp73 during in vitro differentiation of neuroblastoma cells and cortical neurons. Retinoid-driven neuroblastoma differentiation is inhibited by knockdown of either p73 or miR-34a. Transcript expression of miR-34a is significantly reduced in vivo both in the cortex and hippocampus of p73−/− mice; miR-34a and TAp73 expression also increase during postnatal development of the brain and cerebellum when synaptogenesis occurs. Accordingly, overexpression or silencing of miR-34a inversely modulates expression of synaptic targets, including synaptotagmin-1 and syntaxin-1A. Notably, the axis TAp73/miR-34a/synaptotagmin-1 is conserved in brains from Alzheimer's patients. These data reinforce a role for TAp73 in neuronal development.

Item Type: Article
Schools: Schools > School of Environment and Life Sciences
Journal or Publication Title: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
ISSN: 0027-8424
Depositing User: BS Sayan
Date Deposited: 07 Feb 2023 10:38
Last Modified: 07 Feb 2023 10:45

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