Search for microRNA capable of modifying with ADAR2 activity

• Project/Area Number: 19790601
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: The University of Tokyo
• Principal Investigator: YAMASHITA Takenari The University of Tokyo, 医学部附属病院, リサーチ・フェロー (20431843)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥2,570,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: ADAR2 / RNA編集 / 筋萎縮性側索硬化症 / microRNA / AMPA 受容体 / AMPA受容体

Research Abstract

孤発性ALSの運動ニューロン死に深く関わるRNA編集酵素ADAR2活性をin vitroで評価するシステムを開発した。その系を用いADAR2活性に影響を与えた3種のmicroRNAsを同定した。1種はADAR2活性を賦活したが、2種のmicroRNAsはADAR2活性を抑える作用があった。後者2種のmicroRNAsはADAR2 mRNA対GluR2ミニ遺伝子転写物比(酵素対基質量比)依存的にADAR2活性を抑制したが、ADAR2活性賦活の分子メカニズムは明らかにできなかった。microRNAsはADAR2活性に効果を与えることが明らかとなり、ADAR2活性の賦活による孤発性ALSの治療戦略のツールとして、有用であることが期待される。

Research Products

• [Journal Article] Effects of antidepressants on GluR2 Q/R site-RNA editing in modified HeLa cell line. (2009)
  • Author(s): Sawada J, Yamashita T, Aizawa H, Aburakawa Y, Hasebe N, Kwak S
  • Journal Title: Neurosci. Res. in press
  • Peer Reviewed
• [Journal Article] Newly identified ADAR2-mediated editing positions as a useful tool for ALS research. (2008)
  • Author(s): Kwak S, Nishimoto Y, Yamashita T
  • Journal Title: RNA Biology 5 Pages: 193-197
  • Peer Reviewed
• [Journal Article] Determination of editors at the novel A-to-I editing positions (2008)
  • Author(s): Nishimoto Y, Yamashita T, Hideyama T, Tsuji S, Suzuki N, Kwak S
  • Journal Title: Neurosci. Res. 61(2) Pages: 201-206
  • Peer Reviewed
• [Journal Article] Determination of editors at the novel A-to-I editing positions (2008)
  • Author(s): Nishimoto Y., Yamashita T., Hideyama T., Tsuji S., Suzuki N., Kwak S.
  • Journal Title: Neuroscience Research 61 Pages: 201-206
  • Peer Reviewed
• [Journal Article] Newly identified ADAR2-mediated editing positions as a useful tool for ALS research (2008)
  • Author(s): Kwak S., Nishimoto Y., Yamashita T.
  • Journal Title: RNA Biology 5 Pages: 193-197
  • Peer Reviewed
• [Journal Article] Determination of editors at the novel A-to-I editing positions (2008)
  • Author(s): Nishimoto Y., Yamashita T., Hideyama T., Tsuji S. Suzuki N., Kwak S.
  • Journal Title: Neuroscience Research (掲載確定)
• [Journal Article] Effects of antidepressants on GluR2 Q/R site-RNA editing in modified HeLa cellline
  • Author(s): Sawada J., Yamashita T., Aizawa H., Aburakawa Y., Hasebe N., Kwak S.
  • Journal Title: Neuroscience Research (印刷中)
  • Peer Reviewed
• [Presentation] Regulation mechanism of GluR2 Q/R site-editing in cultured cell lines (2008)
  • Author(s): Yamashita T, Tadami C, Nishimoto Y, Hideyama T, Kimura D, Suzuki T, Kwak S
  • Organizer: Society for neuroscience 38th Annual Meeting
  • Place of Presentation: Washington, DC
  • Year and Date: 2008-11-17
• [Presentation] Slow neuronal death of motor neurons in sporadic ALS mouse model by RNA editing enzyme ADAR2 knockout. (2008)
  • Author(s): Hideyama T, Yamashita T, Tsuji S, Takahashi R, Misawa H, Suzuki T, Kwak S
  • Organizer: 38th Annual Meeting Society for Neuroscience
  • Place of Presentation: Washington
• [Presentation] Slow death of motor neurons in sporadic ALS mouse model by conditional targeting of RNA editing enzyme ADAR2 (2008)
  • Author(s): Hideyama T, Yamashita T, Tsuji S, Takahashi R, Misawa H, Suzuki T, Kwak S
  • Organizer: The 19th International Symposium on MND/ALS. 2008
  • Place of Presentation: Birmingham
• [Presentation] Sporadic ALS model mice by RNA editing enzyme abnormality. (2008)
  • Author(s): Hideyama T, Yamashita T, Tsuji S, Takahashi R, Misawa H, Suzuki T, Kwak S
  • Organizer: 6th Forum of European Neuroscience Forum 2008
  • Place of Presentation: Geneve
• [Presentation] 培養細胞によるGluR2 Q/R部位の編集制御機構 (2008)
  • Author(s): 山下雄也, 只見智恵子, 西本祥仁, 日出山拓人, 木村大輔, 鈴木岳之, 郭伸
  • Organizer: 第31回神経科学大会 Neuro2008
  • Place of Presentation: 東京
• [Presentation] RNA編集異常による孤発性筋萎縮性側索硬化症モデルマウスの作製 (2008)
  • Author(s): 郭 伸, 日出山拓人, 山下雄也, 辻省次, 高橋良輔, 三澤日出巳, 木村大輔, 鈴木岳之
  • Organizer: 第31回神経科学大会、Neuro2008
  • Place of Presentation: 東京
• [Presentation] AMPA受容体サブユニットGluR2のQ/R部位RNA編集率に及ぼす各種薬剤の効果 (2008)
  • Author(s): 澤田 潤, 相澤仁志, 山下雄也, 油川陽子, 長谷部直幸, 郭 伸
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] RNA編集異常による孤発性ALSモデルマウスの開発 (2008)
  • Author(s): 日出山拓人, 西本祥仁, 山下雄也, 辻省次, 高橋良輔, 三澤日出巳, 鈴木岳之, 郭 伸
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] Sporadic ALS model mice by RNA editing enzyme abnormality (2008)
  • Author(s): Hideyama T, Yamashita T, Tsuji S, Takahashi R, Misawa H. Suzuki T. Kwak S
  • Organizer: 6^<th> Forum of European Neuroscience Forum 2008
  • Place of Presentation: Geneve, スイス国
• [Presentation] 培養細胞によるGluR2Q/R部位の編集制御機構 (2008)
  • Author(s): 山下雄也, 只見智恵子, 西本祥仁, 日出山拓人, 木村大輔, 鈴木岳之, 郭伸
  • Organizer: 第31回神経科学大会、Neuro2008
  • Place of Presentation: 東京
• [Presentation] Slow death of motor neurons in sporadic ALS mouse model by conditi onal targeting of RNA editing enzyme ADAR2 (2008)
  • Author(s): Hideyama T, Yamashita T, Tsuji S, Takahashi R, Misawa H. Suzuki T, Kwak S
  • Organizer: The 19^<th> International Symposium on MND/ALS
  • Place of Presentation: Birmingham, 英国
• [Presentation] Regulation mechanism of G1uR2 Q/R site-editing in cultured cell lines (2008)
  • Author(s): Yamashita T, Tadami C, Nishimoto Y, Hideyama T, Kimura D, Suzuki T, Kwak S
  • Organizer: Society for neuroscience 38th Annual Meeting
  • Place of Presentation: Washington DC, 米国
• [Presentation] Slow neuronal death of motor neurons in sporadic ALS mouse model by RNA editing enzyme ADAR2 knockout (2008)
  • Author(s): Hideyama T, Yamashita T, Tsuji S, Takahashi R, Misawa H, Suzuki T, Kwak S
  • Organizer: Society for neuroscience 38th Annual Meeting
  • Place of Presentation: Washington DC, 米国
• [Presentation] Establishment of a novel Hela cell line stably expressing the half-echted GluR2 transcript (2007)
  • Author(s): Yamashita T., Tadami C., Nishimoto Y., Kimura D., Suzuki T., Kwak S.
  • Organizer: Society for Neuroscience 37th Annual Meeting
  • Place of Presentation: San Diego, California
  • Year and Date: 2007-11-06
• [Presentation] Tet onシステムを利用したAMPA受容体サブユニットGluR2のRNA編集率測定株の樹立 (2007)
  • Author(s): 山下雄也、只見知恵子、西本祥仁、木村大輔、鈴木岳之、郭伸
  • Organizer: 東京大学生命科学研究ネットワークシンポジウム2007
  • Place of Presentation: 東京
  • Year and Date: 2007-09-15
• [Presentation] Tet Onシステムを利用したRNA編集活性測定株の樹立 (2007)
  • Author(s): 山下雄也、只見知恵子、西本祥仁、木村大輔、鈴木岳之、郭伸
  • Organizer: 第50回日本神経化学会大会合同大会Neuro2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-10
• [Presentation] Establishment of a novel Hela cell line stably expressing the half-edited GluR2 transcript. (2007)
  • Author(s): Yamashita, T, Tadami, C, Nishimoto,Y, Kimura, D, Suzuki,T, Kwak, S
  • Organizer: Society for Neuroscience 37th Annual Meeting, No. 591.16.
  • Place of Presentation: San Diego, California
• [Presentation] Death of motor neurons in mice deficient in an RNA editing enzyme (2007)
  • Author(s): Hideyama, T, Yamashita, T, Tsuji, S, Takahashi, R, Misawa, H, Suzuki, T, Kwak, S
  • Organizer: Amiotroph Later Scl, P153
  • Place of Presentation: Tronto, Canada
• [Presentation] Tet onシステムを利用したRNA編集活性測定株の樹立 (2007)
  • Author(s): 山下雄也, 只見知恵子, 西本祥仁, 木村大輔, 鈴木岳之, 郭伸
  • Organizer: 第50回日本神経化学会(横浜)大会合同大会 Neuro2007、P1-j01
  • Place of Presentation: 横浜
• [Presentation] RNA編集異常による孤発性ALSモデルマウスの開発 (2007)
  • Author(s): 郭伸, 日出山拓人, 西本祥仁, 山下雄也, 辻省次, 高橋良輔, 三澤日出巳, 鈴木岳之
  • Organizer: 第30回日本神経科学会合同大会 Neuro2007、P1-h47
  • Place of Presentation: 横浜
• [Presentation] Alteration of RNA editing and neuronal death in motor neuron diseases. (2007)
  • Author(s): Hideyama, T, Nishimoto, Y, Yamashita, T, Tsuji, S, Takahashi, H, Kakita, A, Suzuki, T, Kwak, S
  • Organizer: ENS 2007, No. 700.
  • Place of Presentation: Rhodes
• [Presentation] 孤発性筋萎縮性側索硬化症のRNA編集異常 (2007)
  • Author(s): 日出山拓人, 西本祥仁, 山下雄也, 伊藤杏子, 辻省次, 高橋良輔, 三澤日出巳, 鈴木岳之, 郭伸
  • Organizer: 第48回日本神経学会総会、No. 10022
  • Place of Presentation: 名古屋
• [Presentation] 孤発性ALSのバイオマーカーの開発 (2007)
  • Author(s): 西本祥仁, 日出山拓人, 山下雄也, 鈴木則宏, 郭伸
  • Organizer: 第48回日本神経学会総会、P-10122
  • Place of Presentation: 名古屋
• [Presentation] グリオーマ細胞におけるAMPA受容体サブユニットGluR2のRNA編集率の検討 (2007)
  • Author(s): 只見智恵子, 木村大輔, 伊藤杏子, 山下雄也, 鈴木岳之, 郭伸
  • Organizer: 第80回日本薬理学会年会、No. 10300
  • Place of Presentation: 名古屋
• [Presentation] 孤発性ALSのバイオマーカーの開発 (2007)
  • Author(s): 西本祥仁、日出山拓人、山下雄也、鈴木則宏、郭 伸
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋
• [Book] AMPA receptor-mediated neuronal death in motor neuron diseases. In: Amino Acid Receptor Research, Eds. Paley BF, Warfield TE (2008)
  • Author(s): Kwak S, Hideyama T, Yamashita T
  • Publisher: Nova Science Publishers Inc. NY.
• [Book] In Amino Acid Receptor Research (AMPA receptor-mediated neuronal death in motor neuron diseases) (2008)
  • Author(s): Kwak S., Hideyama T., Yamashita T
  • Publisher: Nova Science Publishers Inc. NY
• [Book] グルタミン酸受容体と神経細胞死、神経変性疾患のサイエンス (2007)
  • Author(s): 山下雄也, 郭 伸
  • Publisher: 南山堂
• [Book] 神経変性疾患のサイエンス(グルタミン酸受容体と神経細胞死) (2007)
  • Author(s): 山下 雄也, 郭 伸
  • Publisher: 南山堂