Analysis on circular RNAs potentially related to spinocerebellar ataxia type 31.

• Project/Area Number: 15H06181
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Sato Nozomu 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (30754551)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 環状RNA / Non-coding RNA / 神経変性疾患 / 脊髄小脳失調症31型 / Alu / microsatellite / マイクロサテライト伸長 / non-coding RNA

Outline of Final Research Achievements

Circular RNAs (circRNAs) are a type of non-coding RNAs whose functions are yet to be unveiled. Intronic Alu sequences have been shown to be important for the systhesis of circRNAs. We aimed to clarify the effect of microsatellite expansions associated with Alu, which sometimes result in neurodegenerative disorders, on the synthesis and metabolism of circRNAs. The mutation responsible for spinocerebellar ataxia type 31 (SCA31) is an example of such microsatellite expansions, and we tried to identify the effect of the SCA31 mutation on potential circRNAs orginating from BEAN1 and TK2, the genes harboring the SCA31 mutation. We conducted RT-PCR on brain specimens of SCA31 autopsy samples and of mutant human BEAN1 transgenic mice in various conditions, but we could not found DNA fragments resulting from potential circRNAs of BEAN1 and TK2. We could not obtain findings suggesting the involvement of circRNA(s) in the pathogenesis of SCA31.

Research Products

• [Journal Article] Regulatory Role of RNA Chaperone TDP-43 for RNA Misfolding and Repeat-Associated Translation in SCA31 (2017)
  • Author(s): Taro Ishiguro, Nozomu Sato, Morio Ueyama, Nobuhiro Fujikake, Chantal Sellier, Akemi Kanegami, Eiichi Tokuda, Bita Zamiri, Terence Gall-Duncan, Mila Mirceta, Yoshiaki Furukawa, 他８名
  • Journal Title: Neuron Volume: 94 Issue: 1 Pages: 108-124
  • DOI: 10.1016/j.neuron.2017.02.046
  • Peer Reviewed / Open Access / Int'l Joint Research