AUTHOR=Fang Meimiao , Li Yali , Ren Jin , Hu Ronggui , Gao Xiaobo , Chen Liang 

TITLE=Epilepsy-Associated UBE3A Deficiency Downregulates Retinoic Acid Signalling Pathway

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.681295

DOI=10.3389/fgene.2021.681295

ISSN=1664-8021

ABSTRACT=<p>Ubiquitin-protein ligase E3A (UBE3A) has dual functions as a E3 ubiquitin-protein ligase and coactivator of nuclear hormone receptors. Mutations or deletions of the maternally inherited UBE3A gene cause Angelman syndrome. Here, we performed transcriptome profiling in the hippocampus of <italic>Ube3a<sup><italic>m</italic>+/p+</sup></italic> and <italic>Ube3a<sup><italic>m–/p</italic>+</sup></italic> mice, and determined that the expression of the retinoic acid (RA) signalling pathway was downregulated in Ube3a-deficient mice compared to WT mice. Furthermore, we demonstrated that UBE3A directly interacts with RARα and may function as a coactivator of the nuclear receptor RARα to participate in the regulation of gene expression. Loss of UBE3A expression caused the downregulation of the expression of RA-related genes, including <italic>Erbb4, Dpysl3, Calb1, Pten</italic>, and <italic>Arhgap5</italic> in Ube3a<sup><italic>m–/p</italic>+</sup> mice brain tissues. This work revealed a new role for UBE3A in regulating retinoic acid (RA) signalling downstream genes and hopefully to shed light on the potential drug target of AS.</p>