Fang Meimiao, Li Yali, Ren Jin, Hu Ronggui, Gao Xiaobo, Chen Liang
School of Medicine, Guizhou University, Guiyang, China.
State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
Front Genet. 2021 Apr 28;12:681295. doi: 10.3389/fgene.2021.681295. eCollection 2021.
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 and 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 , and in Ube3a 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.
泛素蛋白连接酶E3A（UBE3A）具有作为E3泛素蛋白连接酶和核激素受体共激活因子的双重功能。母系遗传的UBE3A基因突变或缺失会导致天使综合征。在此，我们对野生型和Ube3a缺陷型小鼠的海马体进行了转录组分析，并确定与野生型小鼠相比，维甲酸（RA）信号通路在Ube3a缺陷型小鼠中的表达下调。此外，我们证明UBE3A直接与RARα相互作用，并可能作为核受体RARα的共激活因子参与基因表达的调控。UBE3A表达缺失导致Ube3a缺陷型小鼠脑组织中包括、和在内的RA相关基因表达下调。这项工作揭示了UBE3A在调节维甲酸（RA）信号下游基因方面的新作用，并有望为天使综合征的潜在药物靶点提供线索。
