Analyzing neuronal development through deciphering splicing code

2011 Fiscal Year Final Research Report

• Project/Area Number: 21249013
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kyoto University (2010-2011); Tokyo Medical and Dental University (2009)
• Principal Investigator: HAGIWARA Masatoshi 京都大学, 大学院・医学研究科, 教授 (10208423)
• Co-Investigator(Kenkyū-buntansha): OONO Kinji (80397455) ; TAKEUCHI Akihide (90436618)
• Project Period (FY): 2009 – 2011
• Keywords: スプライシング / 大脳皮質形成 / エクソンアレイ / スプライシング調節因子 / プロファイリング解析

Research Abstract

We could identified genome wide level of alternative splicing regulation regarding spliced genes and RNA-binding proteins during neuronal development.

Research Products

• [Journal Article] CELF family RNA-binding protein UNC-75 regulates two sets of mutually exclusive exons of the unc-32 gene in neuron-specific manners in Caenorhabditis elegans. (2013)
  • Author(s): Kuroyanagi H, Watanabe Y, and Hagiwara M.
  • Journal Title: PLoS Genet Volume: 9(2) Pages: e1003337
  • Peer Reviewed
• [Journal Article] 可視化スプライシング・レポーターシステムで開く哺乳類の mRNA 制御の世界 (2012)
  • Author(s): 武内章英、萩原正敏
  • Journal Title: 細胞工学 Volume: VOl.31 No.6
• [Journal Article] RNA を標的とした新しい創薬戦略 (2012)
  • Author(s): 萩原正敏、片岡直行
  • Journal Title: 実験医学2012 増刊疾患克服をめざしたケミカルバイオロジー Pages: 46-52
• [Journal Article] Muscle - specific splicing factors ASD - 2 and SUP - 12 cooperatively switch alternative pre - mRNA processing patterns of the ADF/cofilin gene in C. elegans . (2012)
  • Author(s): Ohno G , Ono K , Togo M , Watanabe Y , Ono S ,Hagiwara M , Kuroyanagi H
  • Journal Title: PLoS Genet Volume: 8(10) Pages: e1002991
  • Peer Reviewed
• [Journal Article] Stress-responsive maturation of Clk1/4 pre-mRNAs promotes phosphorylation of SR splicing factor. (2011)
  • Author(s): Ninomiya K, Kataoka N, andHagiwara M.
  • Journal Title: J Cell Biol. Volume: 195(1) Pages: 27-40
• [Journal Article] Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing. (2011)
  • Author(s): Debdab M, Carreaux F, Renault S, Soundararajan M, Fedorov O, Filippakopoulos P, Lozach O, Babault L, Tahtouh T, Baratte B, Ogawa Y, Hagiwara M, Eisenreich A, Rauch U, Knapp S, Meijer L, Bazureau JP
  • Journal Title: J Med Chem. Volume: 54(12) Pages: 4172-4186
• [Journal Article] Chemical treatment enhances skipping of a mutated exon in the dystrophin gene. (2011)
  • Author(s): Nishida A, Kataoka N, Takeshima Y, Yagi M, Awano, H, Ota, M, Itoh K, Hagiwara M, and Matsuo M
  • Journal Title: Nature Commun Volume: 2 Pages: 308
• [Journal Article] スプライシング制御機構の解明とその臨床応用 (2010)
  • Author(s): 萩原正敏
  • Journal Title: メディカル・サイエンス・ダイジェスト Volume: Vol.36, No.13 Pages: 2-3
• [Journal Article] RNA スプライシングの可視化による創薬スクリーニング (2010)
  • Author(s): 野島孝之、萩原正敏
  • Journal Title: 細胞工学 Volume: Vol.29, No.02 Pages: 175-180
• [Journal Article] RNA プロセシング異常RNA 病を斬る 基礎の基礎 (2010)
  • Author(s): 萩原正敏
  • Journal Title: 細胞工学 Volume: Vol.29, No.02 Pages: 126-130
• [Journal Article] Splicing reportermice revealed the evolutionally conserved switching mechanism of tissue-specific alternative splicing. (2010)
  • Author(s): Takeuchi A, Hosokawa M, Nojima T, Hagiwara M
  • Journal Title: PLOS One Volume: 5 Pages: e10946
• [Journal Article] Visualization and genetic analysis ofalternative splicing regulation in vivo using fluorescence reporters in transgenic Caenorhabditis elegans. (2010)
  • Author(s): Kuroyanagi H, Ohno G, Sakane, H, Maruoka, H, and Hagiwara M
  • Journal Title: Nature Protoc. Volume: 5 Pages: 1495-1517
• [Journal Article] mRNA スプライシング制御から難治疾患の治療へ (2009)
  • Author(s): 萩原正敏
  • Journal Title: 実験医学 Volume: Vol.27, No.17 Pages: 2870-2875
• [Journal Article] Herpesvirus protein ICP27 switches PML isoform by altering mRNA splicing. (2009)
  • Author(s): Nojima T, Oshiro-Ideue T, Nakanoya H, Kawamura H, Morimoto M, Kawaguchi Y, Kataoka N and Hagiwara M
  • Journal Title: Nucleic. Acids Res. Volume: 37 Pages: 6515-6527
  • Peer Reviewed
• [Presentation] プロテオームの多様性創出のメカニズムについて (2013)
  • Author(s): 萩原正敏
  • Organizer: JHUPO サテライトシンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2013-01-18
• [Presentation] Neural development and splicing code (2012)
  • Author(s): 萩原正敏
  • Organizer: 第35回日本神経科学大会「RNA 結合タンパクと病態シンポジウム」
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-21
• [Presentation] RNA を標的とする創薬によって難治疾患に挑む (2012)
  • Author(s): 萩原正敏
  • Organizer: 第36回阿蘇シンポジウム
  • Place of Presentation: 熊本
  • Year and Date: 2012-08-03
• [Presentation] New chemical screens for drugs of congenital genetic disorders targeting pre-mRNAs (2012)
  • Author(s): Masatoshi Hagiwara
  • Organizer: Gordon Research Conference
  • Place of Presentation: Newport, USA.
  • Year and Date: 2012-07-19
• [Presentation] Challenges to Congenital Genetic Disorders with "RNA-targeting" Chemical Compounds (2012)
  • Author(s): Masatoshi Hagiwara
  • Organizer: The 22^<nd> CDB Meeting
  • Place of Presentation: Kobe
  • Year and Date: 2012-06-11
• [Presentation] Challenges to congenital genetic disorder with"RNA-targeting" chemical compounds (2012)
  • Author(s): Masatoshi Hagiwara
  • Organizer: SLAS2013 2^<nd> Annual Conference &Exhibition
  • Place of Presentation: ORLAND,FL,USA.
  • Year and Date: 2012-01-14
• [Presentation] New therapeutics by alteration of mRNA expression and processing with small chemicals" (2011)
  • Author(s): Masatoshi Hagiwara
  • Organizer: International Chemical Biology Conference
  • Place of Presentation: USA
  • Year and Date: 20111011-12
• [Presentation] Visuali zation of alternative splicing and the therapeutic manipulation with chemical compounds (2011)
  • Author(s): Masatoshi Hagiwara
  • Organizer: US - Japan Sumer Conference
  • Place of Presentation: USA
  • Year and Date: 20110804-05
• [Presentation] Visualization of Alternative Splithin with Multi-color Splicing Reporters and Their Application for Screen of Trans-acting Factors and Small Chemicals (2011)
  • Author(s): 萩原正敏
  • Organizer: The16th Annual Meeting of the RNA Society/The RNA Society of Japan 13^<th> Annual Meeting
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20110614-18
• [Presentation] Modulation of pre-mRNA splicing patterns with synthetic chemicals and their clinical applications (2011)
  • Author(s): Masatoshi Hagiwara
  • Organizer: 第10回上原記念生命科学財団 国際シンポジウム[生体制御分子科学]
  • Place of Presentation: 東京
  • Year and Date: 20110600
• [Presentation] Splicing resume from stress response (2010)
  • Author(s): Masatoshi Hagiwara
  • Organizer: Asian Cold Spring Harbor Laboratory 'RNA Biology'
  • Place of Presentation: Suzhou Dushu Lake Conference Center , China
  • Year and Date: 20101101-05
• [Presentation] Visualizatio and manipulation of RNA splicing to cure RNA diseases (2010)
  • Author(s): Masatoshi Hagiwara
  • Organizer: Gorodon Research Conference
  • Place of Presentation: New port, RI
  • Year and Date: 20100718-23
• [Remarks]
  • URL: http://www.med.kyoto-u.ac.jp/organization-staff/research/doctoral_course/r-002/
• [Patent(Industrial Property Rights)] Transgenic reporter system that reveals expression profiles and regulation mechanisms of alternative splicing in mammalian organisms (2011)
  • Inventor(s): 萩原正敏、武内章英
  • Industrial Property Rights Holder: 萩原正敏、武内章英
  • Industrial Property Number: (US.61/350,420) (PCT/JP2011/003059)
  • Filing Date: 2011-05-31
  • Overseas
• [Patent(Industrial Property Rights)] 遺伝性疾患の予防・改善剤 (2011)
  • Inventor(s): 萩原正敏、片岡直行、松尾雅文、西田篤史
  • Industrial Property Rights Holder: 萩原正敏、片岡直行、松尾雅文、西田篤史
  • Industrial Property Number: (特願 2010-146699)(PCT/JP2011/003655)
  • Filing Date: 2011-06-27