The target gene of Ube3a is implicated in transcriptional regulation

• Project/Area Number: 15K08305
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Furumai Ryohei 国立研究開発法人理化学研究所, 脳科学総合研究センター, 客員研究員 (30450414)
• Co-Investigator(Renkei-kenkyūsha): TAKUMI Toru 国立研究開発法人理化学研究所, 脳科学総合研究センター, チームリーダー (00222092)
• Project Period (FY): 2015-10-21 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 発達障害 / アンジェルマン症候群 / ユビキチン化酵素 / 転写制御 / 遺伝子 / 神経科学 / 生理学 / 脳神経疾患 / 行動学

Outline of Final Research Achievements

UBE3A is a responsible gene for the pathogenesis of Angelman syndrome (AS), a neurodevelopmental disorder. Since UBE3A encodes an E3 ubiquitin ligase, several targets have been identified including synaptic molecules. Although proteolysis occurs mainly in the cytoplasm, UBE3A localizes not only in the cytoplasm but also in the nucleus. In fact, UBE3A has been classically known as a transcriptional regulator of nuclear receptor family. However, the function of UBE3A in the nucleus remains unclear especially in neurophysiology. Thus, we focused on the involvement of UBE3A in transcription in the nuclei of neurons. Genome-wide transcriptome analysis revealed that downstream of Interferon Regulatory Factor (IRF) was changed in UBE3A-deficient AS model mice. In vitro biochemical analyses further demonstrated that UBE3A could enhance IRF-dependent transcription. These results suggested the novel function of UBE3A as a transcriptional regulator of immune system in brain.