Analysis of RNA binding proteins in polyglutamine disease

• Project/Area Number: 26670445
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Yokohama City University
• Principal Investigator: TANAKA Fumiaki 横浜市立大学, 医学(系)研究科(研究院), 教授 (30378012)
• Co-Investigator(Kenkyū-buntansha): DOI Hiroshi 横浜市立大学, 医学部, 講師 (10326035) ; KOYANO Shigeru 横浜市立大学, 医学部, 准教授 (50315818) ; TADA Mikiko 横浜市立大学, 附属病院, 助教 (30722467)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ポリグルタミン病 / PCBP / RNA結合タンパク / 核内封入体

Outline of Final Research Achievements

Using aggregate proteome analysis we identified many component proteins of polyglutamine nuclear aggregates including RNA binding proteins. In this study we analyzed the staining patterns of PCBP1, PCBP2, PCBP3, hnRNPU, hnRNP H1, hnRNP H2, hnRNP F, DDX5, DDX17, Matrin 3, and SGTA in human autopsy brains of various polyglutamine diseases. As a result, Matrin 3 and SGTA were observed in nuclear aggregates. Preliminary result shows that SGTA suppresses aggregate formation in Huntington's disease cell model. Further, we identified SGTA-binding proteins using mass spectrometry.

Research Products

• [Journal Article] Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort (2016)
  • Author(s): Ryoichi Nakamura, Jun Sone, Naoki Atsuta, Genki Tohnai, Hazuki Watanabe, Daichi Yokoi, Masahiro Nakatochi, Hirohisa Watanabe, Mizuki Ito, Jo Senda, Masahisa Katsuno, Fumiaki Tanaka, Yuanzhe Li, Yuishin Izumi, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Satoshi Kuwabara, Koji Abe.
  • Journal Title: Neurobiology of Aging Volume: 39 Pages: 219-219
  • DOI: 10.1016/j.neurobiolaging.2015.11.030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association of multiple sclerosis with lateral olfactory tract usher substance (LOTUS), a possible endogenous inhibitor of axonal degeneration (2015)
  • Author(s): Takahashi K, Takei K, Tanaka F
  • Journal Title: Clin Exp Neuroimmunol Volume: 6 Issue: S1 Pages: 64-69
  • DOI: 10.1111/cen3.12272
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A Japanese case of cerebellar ataxia, spastic paraparesis and deep sensory impairment associated with a novel homozygous TTC19 mutation (2015)
  • Author(s): Kunii M, Doi H, Higashiyama Y, Kugimoto C, Ueda N, Hirata J, Tomita-Katsumoto A, Kashikura-Kojima M, Kubota S, Taniguchi M, Murayama K, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Matsumoto N, Tanaka F.
  • Journal Title: J Hum Genet Volume: 60 Issue: 4 Pages: 187-191
  • DOI: 10.1038/jhg.2015.7
  • NAID: 40020433141
  • Peer Reviewed / Open Access
• [Journal Article] Quantitative analysis of intraneuronal transport in human iPS neurons (2015)
  • Author(s): Nakamura H, Yamashita N, Kanamaru Y, Tachibana T, Sekino Y, Chen S, Gotoh T, Tanaka F, Goshima Y
  • Journal Title: J Pharmacol Sci Volume: 128 Issue: 4 Pages: 170-178
  • DOI: 10.1016/j.jphs.2015.06.006
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Neuropathological staging of spinocerebellar ataxia type 2 by semiquantitative 1C2-positive neuron typing Nuclear translocation of cytoplasmic 1C2 underlies disease progression of spinocerebellar ataxia type 2. (2014)
  • Author(s): Koyano S, Yagishita S, Kuroiwa Y, Tanaka F, Uchihara T.
  • Journal Title: Brain Pathol Volume: 26 Issue: 6 Pages: 599-606
  • DOI: 10.1111/bpa.12146
  • Peer Reviewed
• [Journal Article] Late-onset spastic ataxia phenotype in a patient with a homozygous DDHD2 mutation (2014)
  • Author(s): Doi H, Ushiyama M, Baba T, Tani K, Shiina M, Ogata K, Miyatake S, Yuzawa YF, Tsuji S, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Ikeda S, Tanaka F, Matsumoto N, Yoshida K
  • Journal Title: Sci Rep Volume: 4 Issue: 1 Pages: 7132-7132
  • DOI: 10.1038/srep07132
  • NAID: 120007100602
  • Peer Reviewed / Open Access
• [Journal Article] Schwann cell involvement in the peripheral neuropathy of spinocerebellar ataxia type 3. (2014)
  • Author(s): Suga N, Katsuno M, Koike H, Banno H, Suzuki K, Hashizume A, Mano T, Iijima M, Kawagashira Y, Hirayama M, Nakamura T, Watanabe H, Tanaka F, Sobue G
  • Journal Title: Neuropathol Appl Neurobiol. Volume: 40 Issue: 5 Pages: 628-639
  • DOI: 10.1111/nan.12055
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 孤発性筋萎縮性側索硬化症におけるMatrin3の病理学的検討 (2015)
  • Author(s): 多田 美紀子、土井 宏、児矢野 繁、田中 章景
  • Organizer: 第56回日本神経病理学会総会
  • Place of Presentation: 九州大学医学部百年講堂(福岡県福岡市東区)
  • Year and Date: 2015-06-03
• [Presentation] SCA2病変におけるTDP-43細胞内局在 (2015)
  • Author(s): 児矢野 繁、多田 美紀子、柳下 三郎、内原 俊記、田中 章景
  • Organizer: 第56回日本神経病理学会総会
  • Place of Presentation: 九州大学医学部百年講堂(福岡県福岡市東区)
  • Year and Date: 2015-06-03
• [Presentation] Late-onset spastic ataxia phenotype related to a novel homozygous DDHD2 mutation (2015)
  • Author(s): 土井 宏、吉田 邦広、牛山 雅夫、谷 佳津子、松本 直通、田中 章景
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ(新潟県新潟市中央区)
  • Year and Date: 2015-05-20
• [Presentation] RNA病からみた認知症関連疾患 C9orf72遺伝子変異と前頭側頭型認知症 (2014)
  • Author(s): 田中章景
  • Organizer: 第33回日本認知症学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-29 – 2014-12-01
  • Invited
• [Presentation] Analysis of major amyotrophic lateral sclerosis genes in Japan (2014)
  • Author(s): Nakamura R, Sone J, Atsuta N, Watanabe H, Hirakawa A, Watanabe H, Ito M, Senda J, Katsuno K, Tanaka F, Izumi Y, Morita M, Ogaki K, Taniguchi A, Aiba A, Mizoguchi K, Okamoto K, Hasegawa K, Aoki M, Kawata A, Abe K, Oda M, Konagaya M, Imai T, Nakagawa M, Tsuji S, Kaji R, Nakano I, Sobue G
  • Organizer: 64th Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: San Diego Convention Center, San Diego, CA, USA
  • Year and Date: 2014-10-18 – 2014-10-22