Structural study of the disease-related splicing regulatory factors

• Project/Area Number: 23370080
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Musashino University (2013); The Institute of Physical and Chemical Research (2011-2012)
• Principal Investigator: MUTO Yutaka 武蔵野大学, 薬学研究所, 教授 (30192769)
• Project Period (FY): 2011-11-18 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000); Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: 選択的スプライシング / 構造生物学 / NMR / 制御因子 / スプライシング / 前頭側頭型痴呆症 / RNA結合蛋白質 / Tra2β / ＮＭＲ / 超遠心分析 / ＩＴＣ / helicase / ITC / SF2 / SFM

Research Abstract

Splicing reactions plays an important role in the regulation of the biological system. For the elucidation of its regulatory mechanism, the DNA sequence information is not enough and the structural information for the related splicing regulatory factors is necessary. First, in the present study, structural basis for the intermolecular coordination between multi splicing factors is investigated. Here we determined solution structure of a ternary complex composed of the RNA recognition motif (RRM) domains from an RBFOX family protein ASD-1 and a SUP-12-RBM24-RBM38 family member SUP-12 for the alternative splicing of the sole FGFR gene egl-15.The two RRM domains cooperatively interact with the RNA by sandwiching a guanine base to form the stable complex. In addition, investigation of the Tra2-b splicing factor and the target RNA revealed that the ternary and secondary structure of the target RNA affect the binding specificity to the corresponding splicing regulatory factors.

Research Products

• [Journal Article] Aberrant assembly of RNA recognition motif 1 links to pathogenic conversion of TAR DNA-binding protein of 43 kDa (TDP-43) (2013)
  • Author(s): Shodai A, Morimura T, Ido A, Uchida T, Ayaki T, Takahashi R, Kitazawa S, Suzuki S, Fig.1 a:ternary complex b:SUP-12/RNA binary complex c: 模式図Shirouzu M, Kigawa T, Muto Y, Yokoyama S, Takahashi R, Kitahara R, Ito H, Fujiwara N, Urushitani M
  • Journal Title: J Biol Chem Volume: 288 Pages: 14886-905
• [Journal Article] 1H, 13C, and 15N resonance assignments of the dsRBDs of mouse RNA helicase A (2013)
  • Author(s): Takashi Nagata T, Kengo Tsuda, Naohiro Kobayashi, Peter Guntert, Shigeyuki Yokoyama, and Yutaka Muto
  • Journal Title: Biomolecular NMR Assignment Volume: 7巻 Issue: 1 Pages: 69-72
  • DOI: 10.1007/s12104-012-9380-3
  • Peer Reviewed
• [Journal Article] Aberrant assembly of RNA-recognition motif 1 links to pathogenic conversion of TAR DNA-binding protein-43 (TDP-43) (2013)
  • Author(s): Shodai A, Morimura T, Ido A, Uchida T, Ayaki T, Takahashi R, Kitazawa S, Suzuki S, Shirouzu M, Kigawa T, Muto Y, Yokoyama S, Takahashi R, Kitahara R, Ito H, Fujiwara N, Urushitani M
  • Journal Title: J Biol Chem Volume: 288(21) Issue: 21 Pages: 14886-14905
  • DOI: 10.1074/jbc.m113.451849
  • Peer Reviewed / Open Access
• [Journal Article] Aberrant assembly of RNA-recognition motif 1 links to pathogenic conversion of TAR DNA-binding protein-43 (TDP-43). (2013)
  • Author(s): Shodai A, Morimura T, Ido A, Uchida T, Ayaki T, Takahashi R, Kitazawa S, Suzuki S, Shirouzu M, Kigawa T, Muto Y, Yokoyama S, Takahashi R, Kitahara R, Ito H, Fujiwara N, Urushitani M.
  • Journal Title: J Biol Chem. Volume: PMID:23558684
  • Peer Reviewed
• [Journal Article] Structural insight into the interaction of ADP-ribose with the PARP WWE domains (2012)
  • Author(s): He F, Tsuda K, Takahashi M, Kuwasako K, Terada T, Shirouzu M, Watanabe S, Kigawa T, Kobayashi N, Güntert P, Yokoyama S, Muto Y
  • Journal Title: FEBS Lett Volume: 586 Pages: 3858-3864
  • Peer Reviewed
• [Journal Article] Solution structures of the double-stranded RNA-binding domains from RNA helicase A (2012)
  • Author(s): Nagata T, Tsuda K, Kobayashi N, Shirouzu M, Kigawa T, Güntert P, Yokoyama S, Muto Y
  • Journal Title: Proteins Volume: 80 Pages: 1699-706
  • Peer Reviewed
• [Journal Article] Solution Structure of the Splicing Factor Motif (SFM) of the human Prp18 protein PROTEINS (2012)
  • Author(s): He, F., Makoto Inoue, M., Kigawa, T., Takahashi, M., Kuwasako, K., Tsuda, K., Kobayashi, N., Terada, T., Shirouzu, M., Güntert, P., Yokoyama, S. and Muto, Y
  • Journal Title: Structure, Function, and Bioinformatics Volume: 80 Pages: 968-974
  • Peer Reviewed
• [Journal Article] Structural insight into RNA recognition motifs : Versatile molecular Lego building blocks for biological systems (2012)
  • Author(s): Yutaka Muto and Shigeyuki Yokoyama
  • Journal Title: WIREs RNA (Wiley On line library) Volume: 3 Pages: 229-246
  • Peer Reviewed
• [Journal Article] Solution structures of the double-stranded RNA-binding domains from RNA helicase A (2012)
  • Author(s): Takashi Nagata, et al
  • Journal Title: PROTEINS Volume: (in press)
  • Peer Reviewed
• [Journal Article] Solution structure of the Splicing Factor Motif (SFM) of the human Prp18 protein (2012)
  • Author(s): He, F., Inoue, M., Kigawa, T., Takahashi, M., Kuwasako, K., Tsuda, K., Kobayashi, N., Terada, T., Shirouzu, M., Tanaka, A., Sugano, S., Guntert, P., Yokoyama, S., Muto, Y.
  • Journal Title: Proteins Volume: 80 Issue: 3 Pages: 968-974
  • DOI: 10.1002/prot.24003
  • Peer Reviewed
• [Journal Article] Structures of the first and second double-stranded RNA-binding domains of human TAR RNA-binding protein (2011)
  • Author(s): Yamashita, S., Nagata, T., Kawazoe, M., Takemoto, C., Kigawa, T., Güntert, P., Kobayashi, N., Terada, T., Shirouzu, M., Wakiyama, M., Muto, Y., and Yokoyama S
  • Journal Title: Protein Science Volume: 20 Pages: 118-130
  • Peer Reviewed
• [Journal Article] Structural basis for the dual RNA-recognition modes of human Tra2-・RRM (2011)
  • Author(s): Tsuda, K., Someya T., Kuwasako K., Takahashi M., He F., Unzai S., Inoue M., Harada T., Watanabe S., Terada T., Kobayashi N., Shirouzu M., Kigawa T., Tanaka A., Sugano S., Güntert P., Yokoyama S. and Muto Y.
  • Journal Title: Nucleic Acids Res Volume: 39 Pages: 1538-1553
  • Peer Reviewed
• [Presentation] RNA recognition mode of the RNA recognition motif (RRM) of the human spliceosomal protein (2013)
  • Author(s): 行木-桑迫 香奈子 佐藤敦子 津田健吾 高橋真梨 井上真 寺田貴帆 木川 隆則 白水美香子 行木信一 若松馨 高橋征三 横山茂之 武藤 裕
  • Organizer: 第36回分子生物学会年会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 二つのCCHC-タイプのZinc Fingerドメインをもつタンパク質のRNA認識機構 (2011)
  • Author(s): 高橋真梨
  • Organizer: MBSJ2011
  • Place of Presentation: Yokohama
  • Year and Date: 2011-12-16
• [Presentation] 脊髄性筋萎縮症に関わるスプライシング因子の機能解析 (2011)
  • Author(s): 津田健吾
  • Organizer: MBSJ2011
  • Place of Presentation: Yokohama
  • Year and Date: 2011-12-16
• [Presentation] mRNA前駆体スプライシングに関わるタンパク質のRRMドメインによるRNA認識 (2011)
  • Author(s): 桑迫香奈子
  • Organizer: MBSJ2011
  • Place of Presentation: Yokohama
  • Year and Date: 2011-12-16
• [Presentation] RNA recognition mode of the RNA recognition motif (RRM) of the human spliceosomal protein
  • Author(s): 行木-桑迫 香奈子 佐藤敦子 津田 健吾 高橋真梨 井上真 寺田 貴帆 木川 隆則 白 水美香子行木信一, 若松馨, 高橋征三, 横山茂之, 武藤裕
  • Organizer: 36回分子生物学会年会
  • Place of Presentation: 神戸国際会議場ポートピアホール
• [Presentation] PARP11 WWEドメインによるADP-リボース認識機構の解明
  • Author(s): Fuhu He, 津田健吾, 高橋真梨, 桑迫香奈子, 寺田貴帆, 白水美香子, 渡部暁, 木川隆則, 小林直宏, PeterGüntert, 横山茂之, 武藤裕
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
• [Presentation] mRNA前駆体スプライシングに関わるタンパク質のRRMドメインによるRNA認識
  • Author(s): 桑迫香奈子, 佐藤敦子, 井上真, 寺田貴帆, 白水美香子, 木川隆則, 高橋征三, 横山茂之, 武藤裕
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 脊髄性筋萎縮症に関わるスプライシング因子の機能解析
  • Author(s): 津田健吾, 何発虎, 白水美香子, 寺田貴帆, 井上真, 木川隆則, 横山茂之, 武藤裕
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 二つのCCHC-タイプのZincFingerドメインをもつタンパク質のRNA認識機構
  • Author(s): 高橋真梨, 染谷龍彦, 坂本泰一, 平川真未, 桑迫香奈子, 津田健吾, 何発虎, 渡部暁, 原田拓志, 井上真, 寺田貴帆, 白水美香子, 木川隆則, 河合剛太, 横山茂之, 武藤裕
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Structural Basis for the Dual RNA-recognition Modes of human Tra2-・ RRM
  • Author(s): Tsuda K, Someya T, Kuwasako K, Takahashi M, He F, Unzai S, Inoue M, Harada T, Watanabe S, Terada T, Kobayashi N, Shirouzu M, Kigawa T, Tanaka A, Sugano S, Guntert P, Yokoyama S and Muto Y
  • Organizer: The 16th Annual Meeting of the RNA Society
  • Place of Presentation: Kyoto International Conference Center, Kyoto
• [Book] Wiley Interdiscip Rev RNA (2012)
  • Author(s): Muto Y, Yokoyama S.
  • Publisher: Structural insight into RNA recognition motifs: versatile molecular Lego building blocks for biological systems.
• [Book] WIREs RNA : Structural insight into RNA recognition motifs : Versatile mole cular Lego building blocks for biological systems doi : 10.1002/wrna.1107 (2012)
  • Author(s): Yutaka Muto, et al
  • Publisher: Wiley On line library
• [Remarks]
  • URL: http://www.musashino-u.ac.jp/facilities/pharmacy/bukka.html