RNA metabolism and RNA-binding proteins in polyglutamine diseases

• Project/Area Number: 23791007
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KINO Yoshihiro 独立行政法人理化学研究所, 脳科学総合研究センター, 客員研究員 (80415140)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経変性疾患 / ポリグルタミン / RNA結合タンパク質 / 凝集体 / リピート伸長疾患

Research Abstract

Polyglutamine diseases, including Huntington's disease, are genetic disorders caused by a repeat expansion of CAG repeat tracts in protein-coding regions. This study revealed aberrant RNA processing in polyglutamine diseases using cultured cells and disease model mice, suggesting the involvement of RNA-binding proteins in the disease pathogenesis. In addition, RNA-binding proteins have a potential regulatory role in the expression of the gene products of a polyglutamine disease.

Research Products

• [Journal Article] Dexamethasone induces heat shock response and slows down disease progression in mouse and fly models of Huntington's disease (2014)
  • Author(s): Maheshwari M, Bhutani S, Das A, Mukherjee R, Sharma A, Kino Y, Nukina N, Jana NR
  • Journal Title: Human Molecular Genetics Volume: 23(10) Pages: 2737-2751
• [Journal Article] Cyclin-dependent kinase 5 phosphorylates and induces the degradation of ataxin-2 (2014)
  • Author(s): Asada, A., Yamazaki, R., Kino, Y., Saito, T., Kimura, T., Miyake, M., Hasegawa, M., Nukina, N. & Hisanaga, S.
  • Journal Title: Neurosci. Lett. Volume: 563 Pages: 112-117
  • DOI: 10.1016/j.neulet.2014.01.046
  • Peer Reviewed
• [Journal Article] FUS/TLS医学のあゆみ医学 (2014)
  • Author(s): 紀嘉浩、貫名信行
  • Journal Title: 医療のいまがわかるキーワード2014 Volume: 249(5) Pages: 438-438
• [Journal Article] Dexamethasone induces heat shock response and slows down disease progression in mouse and fly models of Huntington's disease (2014)
  • Author(s): Maheshwari, M., Bhutani, S., Das, A., Mukherjee, R., Sharma, A., Kino, Y., Nukina, N. & Jana, N.R.
  • Journal Title: Hum. Mol. Genet. Volume: 23 Issue: 10 Pages: 2737-2751
  • DOI: 10.1093/hmg/ddt667
  • Peer Reviewed
• [Journal Article] FUS/TLS (2014)
  • Author(s): 紀 嘉浩、貫名 信行
  • Journal Title: 医学のあゆみ 医学・医療のいまがわかるキーワード 2014 Volume: 249 Pages: 438-438
• [Journal Article] ハンチントン病の治療法開発とモデルマウスを用いた評価実験医学 in vivo (2012)
  • Author(s): 紀嘉浩、貫名信行
  • Journal Title: 実験医学によるサイエンスと疾患解明 Volume: Vol. 30 No. 2 (増刊) Pages: 203-210
• [Journal Article] ハンチントン病の治療法開発とモデルマウスを用いた評価 (2012)
  • Author(s): 紀 嘉浩、貫名 信行
  • Journal Title: 実験医学増刊号｢in vivo実験医学によるヒト疾患解明の最前線｣ Volume: 30 Pages: 203-210
• [Journal Article] Alternative splicing of myomesin 1 gene is aberrantly regulated in myotonic dystrophy type 1 (2011)
  • Author(s): Koebis M, Ohsawa N, Kino Y, Sasagawa N, Nishino I, Ishiura S
  • Journal Title: Genes to Cells Volume: 16(9) Pages: 961-972
• [Journal Article] Alternative splicing of myomesin 1 gene is aberrantly regulated in myotonic dystrophy type 1. (2011)
  • Author(s): Koebis M, Ohsawa N, Kino Y, Sasagawa N, Nishino I, Ishiura S.
  • Journal Title: Genes to Cells Volume: 16(9) Issue: 9 Pages: 961-972
  • DOI: 10.1111/j.1365-2443.2011.01542.x
  • Peer Reviewed
• [Presentation] Protein/RNA aggregation in neurological disorders (2013)
  • Author(s): Kino Y, Nukina N
  • Organizer: Neuro2013
  • Place of Presentation: 京都
  • Year and Date: 2013-06-21
• [Presentation] Nuclear localization of MBNL1 : Implications for splicing-mediated autoregulation and expanded repeat-related protein expression (2011)
  • Author(s): Kino Y, Washizu C, Kurosawa M, Oma Y, Ishiura S, Nukina N
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-13
• [Presentation] Muscleblind proteins repress aberrant protein expression derived from expanded repeats (2011)
  • Author(s): Kino Y, Washizu C, Kurosawa M, Oma Y, Ishiura S, Nukina N
  • Organizer: 8th International Myotonic Dystrophy Consortium Meeting
  • Place of Presentation: タンパ(米国)
  • Year and Date: 2011-12-01
• [Presentation] RNA結合タンパク質MBNL1によるリピート伸長疾患RNAの制御 (2011)
  • Author(s): 紀嘉浩、鷲頭知花、黒澤大、貫名信行
  • Organizer: 包括型脳科学推進支援ネットワーク夏のワークショップ
  • Place of Presentation: 神戸
  • Year and Date: 2011-08-23
• [Presentation] 筋萎縮性側索硬化症に関連する変異はFUS/TLSの細胞内局在およびスプライシング制御能に影響する (2011)
  • Author(s): 紀嘉浩、鷲頭知花、奥野弥佐子、黒澤大、山田みず樹、土井宏、貫名信行
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-18
• [Presentation] 筋萎縮性側索硬化症に関連する変異はFUS/TLSの細胞内局在およびスプライシング制御に影響する (2011)
  • Author(s): 紀嘉浩、鷲頭知花、奥野弥佐子、黒沢大、山田みず樹、土井宏、貫名信行
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
• [Presentation] RNA結合タンパク質MBNL1によるリピート伸長疾患RNAの制御 (2011)
  • Author(s): 紀 嘉浩、鷲頭 知花、黒澤 大、貫名 信行
  • Organizer: 包括型脳科学研究推進支援ネットワーク 夏のワークショップ
  • Place of Presentation: 神戸
• [Presentation] Muscleblind proteins repress aberrant protein expression derived from expanded repeats (2011)
  • Author(s): Yoshihiro Kino, Chika Washizu, Masaru Kurowasa, Yoko Oma, Shoichi Ishiura, Nobuyuki Nukina
  • Organizer: 8th International Myotonic Dystrophy Consortium Meeting
  • Place of Presentation: タンパ
• [Presentation] Nuclear Localization of MBNL1: Implications for splicing-mediated autoregulation and expanded repeat-related protein expression (2011)
  • Author(s): Yoshihiro Kino, Chika Washizu, Masaru Kurosawa, Yoko Oma, Shoichi Ishiura, Nobuyuki Nukina
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Protein/RNA aggregation in neurological disorders
  • Author(s): Yoshihiro Kino, Nobuyuki Nukina
  • Organizer: Neuro2013
  • Place of Presentation: 京都
  • Invited
• [Book] モデル動物実験マニュアル疾患モデルの作成と利用脳・神経疾患第2節ハンチントン病モデルマウス (2011)
  • Author(s): 紀嘉浩、黒澤大、貫名信行(分担執筆:三品昌美編)
  • Publisher: 株式会社エル・アイ・シー
• [Book] モデル動物実験マニュアル 疾患モデルの作成と利用 脳・神経疾患 (第2節 ハンチントン病モデルマウス) (2011)
  • Author(s): 紀 嘉浩、黒澤 大、貫名 信行 (分担執筆・三品昌美編)
  • Publisher: 株式会社 エル・アイ・シー