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

Agostini, M; Tucci, P; Killick, R; Candi, E; Sayan, BS

Abstract

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.

Citation

Agostini, M., Tucci, P., Killick, R., Candi, E., & Sayan, B. (2011). Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets. Proceedings of the National Academy of Sciences, 108(52), https://doi.org/10.1073/pnas.1112061109

• Journal Article Type: Article
• Online Publication Date: Dec 12, 2011
• Publication Date: Dec 12, 2011
• Deposit Date: Feb 7, 2023
• Publicly Available Date: Feb 7, 2023
• Journal: Proceedings of the National Academy of Sciences
• Electronic ISSN: 1091-6490
• Publisher: National Academy of Sciences
• Volume: 108
• Issue: 52
• DOI: https://doi.org/10.1073/pnas.1112061109
• Publisher URL: https://doi.org/10.1073/pnas.1112061109