Generation of tRNA neurobiology

• Project/Area Number: 17K19468
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Neuroscience and related fields
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: TANAKA Motomasa 国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (40321781)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 翻訳 / tRNA / mRNA / 神経細胞 / コドン / リボソーム / バイオテクノロジー

Outline of Final Research Achievements

Translation of mRNA is involved in mental function. However, it remains unclear what tRNA species are incorporated into ribosome for translation due to the lack of technology. Here we developed a novel deep sequencing technology and bioinformatics tools to examine roles of tRNA in translation. We revealed by this technology that distinct tRNA species and specific synaptic genes with altered translation rhythms are associated with pathogenesis of human brain disorders.

Academic Significance and Societal Importance of the Research Achievements

翻訳の異常は認知や記憶の障害などの精神機能の異常につながるため、本研究で見出した成果は、新たな疾患治療薬の開発に道を拓くと考えられる。さらには、本研究で開発した新たな網羅的な塩基配列解析技術およびバイオインフォマティクス技術は、神経疾患研究を含む神経科学研究に広く応用が可能である。したがって、翻訳異常がその病態発症に関わると示唆されている神経系疾患のモデルマウスや神経細胞に将来適用することで、それら疾患の発症機序の解明に役立つと期待される。

Research Products

• [Int'l Joint Research] ジョンズホプキンス大学(米国)
• [Int'l Joint Research] ユニバーシティカレッジ・ロンドン(英国)
• [Journal Article] Translation from the ribosome to the clinic: Implication in neurological disorders and new perspectives from recent advances. (2019)
  • Author(s): Hui, K.K., Chen, Y., Endo, R., Tanaka, M.
  • Journal Title: Biomolecules Volume: 9 Issue: 11 Pages: 680-680
  • DOI: 10.3390/biom9110680
  • Peer Reviewed / Open Access
• [Journal Article] TAR DNA-Binding Protein 43 and Disrupted in Schizophrenia 1 Coaggregation Disrupts Dendritic Local Translation and Mental Function in Frontotemporal Lobar Degeneration. (2018)
  • Author(s): Endo R, Takashima N, Nekooki-Machida Y, Komi Y, Hui KK, Takao M, Akatsu H, Murayama S, Sawa A, Tanaka M.
  • Journal Title: Biol Psychiatry. Volume: 84(7) Issue: 7 Pages: 509-521
  • DOI: 10.1016/j.biopsych.2018.03.008
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Impaired mRNA translation and mental function by protein aggregation in neuropsychiatric disorders (2019)
  • Author(s): Motomasa Tanaka
  • Organizer: The 42nd Annual Meeting of the Japanese Neuroscience Society
  • Invited
• [Presentation] タンパク質の凝集化と精神・神経変性疾患 (2019)
  • Author(s): 田中元雅
  • Organizer: The 42nd Annual Meeting of the Japanese Neuroscience Society
  • Invited
• [Presentation] タンパク質の凝集化に着目した 精神・神経変性疾患の病態解明 (2019)
  • Author(s): 田中元雅
  • Organizer: Chemistry for Neuroscience
  • Invited
• [Presentation] TDP-43 and DISC1 Co-Aggregation Disrupts Dendritic Local Translation and Mental Function in FTLD (2018)
  • Author(s): Motomasa Tanaka
  • Organizer: International Symposium on “Proteins; from the Cradle to the Grave”
  • Int'l Joint Research / Invited
• [Book] Make Life Visible (2019)
  • Author(s): Endo, R., Takashima, N., Tanaka, M. (Toyama, Y., Miyawaki, A., Nakamura, M., Jinzaki, M. (eds))
  • Total Pages: 285
  • Publisher: Springer, Singapore
  • ISBN: 9789811379086
• [Remarks] タンパク質の共凝集化による精神障害の発現
  • URL: http://www.riken.jp/pr/press/2018/20180614_1/