Molecular basis of the splicing regulators that are related to the diseases.

• Project/Area Number: 20310141
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: MUTO Yutaka The Institute of Physical and Chemical Research, RNA生物学研究チーム, チームリーダー (30192769)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2010: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000); Fiscal Year 2009: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000); Fiscal Year 2008: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: スプライシング / 前頭側頭型痴呆症 / 筋強直性ジストロフィー / RNA結合蛋白質 / CUG-BP1 / MBNL / Tra2β / NMR / 超遠心分析 / ITC / TRBP / U1 snRNP / 質量分析 / U2 snRNP / CCCHタイプ亜鉛結合ドメイン / TIA1蛋白質 / p14

Research Abstract

In eukaryotic cells, the pre-mRNA splicing reaction plays a crucial role in the regulation of the biological systems. In the present study, we have investigated the protein-protein and/or protein-RNA interactions of the splicing constitutive (U1/U2 snRNP) and the regulatory factors (especially those related to DM and FTD) on the structural point of view.

Research Products

• [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., Kawazo M., Takemoto C., Kigawa T., Guntert P., Kobayashi N., Terada T., Shirouzu M., Wakiyama M., Muto Y., Yokoyama S.
  • Journal Title: Protein Science 20 Pages: 118-130
  • Peer Reviewed
• [Journal Article] Structural basis for the dual RNA-recogniton mode of hman Ta2-β 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., Guntert P., Yokoyama S., Muto Y.
  • Journal Title: Nucleic Acids Res 39 Pages: 1538-1553
  • 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, et al.
  • Journal Title: Protein Science Volume: 20 Pages: 118-130
  • Peer Reviewed
• [Journal Article] Structural basis for the dual RNA-recognition modes of human Tra2-βRRM (2011)
  • Author(s): Tsuda, K., et al.
  • Journal Title: Nucleic Acids Res. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Structural Insight into the Zinc Finger CW Domain as a Histone Modification Reader (2010)
  • Author(s): He, F, et al.
  • Journal Title: Structure Volume: 18 Pages: 1127-1139
  • Peer Reviewed
• [Journal Article] Isoforms of U1-70K control subunit dynamics in the human spliceosomal U1 snRNP. (2009)
  • Author(s): Hernadez H., Makorova OV., Makorova EM., Morqner N., Muto Y., Krummel DP., Robinson CV.
  • Journal Title: Plos One 4
  • Peer Reviewed
• [Journal Article] Structural basis for the sequence-specific RNA-recognition mechanism of human CUG-BP1 RRM3 (2009)
  • Author(s): Tsuda K, Kuwasako K, Takahashi M, Someya T, Inoue M, Terada T, Kobayashi N, Shirouzu M, Kigawa T, Tanaka A, Sugano S, Guntert P, Muto Y, Yokoyama S.
  • Journal Title: Nucleic Acids Res. 37 Pages: 5151-5155
  • Peer Reviewed
• [Journal Article] Characterization of a heat-stable enzyme possessing GTP-dependent RNA ligase activity from a hyperthermhilic archaeon (2009)
  • Author(s): Kanai A., Sato A., Fukuda Y., Okada K., Matsuda T., Sakamoto T., Muto Y., Yokoyama S., Kawai G., Tomita M.
  • Journal Title: Pyrococcus furiosus.RNA 15 Pages: 420-431
  • Peer Reviewed
• [Journal Article] Solution structure of the RNA binding domain in the human muscleblind-like protein 2. (2009)
  • Author(s): He F., Dang W., Abe C., Tsuda K., Inoue M., Watanabe S., Kobayashi N., Kigawa T., Matsuda T., Yabuki T., Aoki M., Seki E., Harada T., Tomabechi Y., Terada T., Shirouzu M., Tanaka A., Guntert P., Muto Y.,, Yokohama S.
  • Journal Title: Protein Science 18 Pages: 81-90
  • Peer Reviewed
• [Journal Article] AU-rich RNA-binding induces changes in the quaternary structure of AUH (2009)
  • Author(s): Kurimoto K., Kuwasako K., Sandercock AM. Unzai S., Robinson, CV. Muto Y., Yokohama S.
  • Journal Title: Proteins 75 Pages: 360-72
  • Peer Reviewed
• [Journal Article] Solution Structure of the GUCT Domain from Human RNA Helicase II/Guβ Reveals the RRM Fold, but Implausible RNA Interactions (2009)
  • Author(s): Ohnishi S., Paakkonen K., Koshiba S., Tochio N., Sato M., Kobayashi N., Harada T., Watanabe S., Muto Y., Guntert P., Tanaka A., Kigawa T., Yokoyama S.
  • Journal Title: Proteins 74 Pages: 133-144
  • Peer Reviewed
• [Journal Article] Isoforms of U1-70K control subunit dynamics in the human spliceosomal U1 sn RNP (2009)
  • Author(s): Hernadez H., et al.
  • Journal Title: Pros One 4
  • Peer Reviewed
• [Journal Article] Structural and functional characterization of the NHR1 domain of the Drosophila Neuralized E3 ligase in the Notch signaling pathway (2009)
  • Author(s): He F., et al.
  • Journal Title: J.M.B 393 Pages: 478-495
  • Peer Reviewed
• [Journal Article] Structural basis for the sequence-specific RNA-recognition mechanism of human CUG-BP1 RRM3 (2009)
  • Author(s): Tsuda K., et al.
  • Journal Title: Nucleic Acids Res. 37 Pages: 5151-6155
  • Peer Reviewed
• [Journal Article] Characterization of a heat-stable enzyme possessing GTP-dependent RNA ligase activity from a hyperthermophilic archaeon, Pyrococcus furiosus (2009)
  • Author(s): Kanai A., et al.
  • Journal Title: RNA 15 Pages: 420-431
  • Peer Reviewed
• [Journal Article] Solution structure of the cysteine-rich domain in Fn14, a member of the tumor necrosis factor receptor superfamily (2009)
  • Author(s): He F., et al.
  • Journal Title: Protein Science 18 Pages: 650-656
  • Peer Reviewed
• [Journal Article] Solution structure of the RNA binding domain in the human muscleblind-like protein 2 (2009)
  • Author(s): He F., et al.
  • Journal Title: Protein Science 18 Pages: 81-90
  • Peer Reviewed
• [Journal Article] AU-rich RNA-binding induces changes in the quaternary structure of AUH (2009)
  • Author(s): Kurimoto K., et al.
  • Journal Title: Proteins 75 Pages: 360-372
  • Peer Reviewed
• [Journal Article] Solution Structure of the GUCT Domain from Human RNA Helicase II/Guβ Reveals the RRM Fold, but Implausible RNA Interactions (2009)
  • Author(s): Ohnishi S., et al.
  • Journal Title: Proteins 74 Pages: 133-144
  • Peer Reviewed
• [Journal Article] The RRM domain of poly(A)-specific ribonuclease has a noncanonical binding site for mRNA cap analog recognition. (2008)
  • Author(s): Nagata T., Suzuki S., Endo R., Shirouzu M., Terada T., Inoue M., Kigawa T., Kobayashi N., Guntert P., Tanaka A., Hayashizaki Y., Muto Y., Yokoyama S.
  • Journal Title: Nucleic Acids Res. 36 Pages: 4754-4767
  • Peer Reviewed
• [Journal Article] Solution structure of the second RNA recognition motif (RRM) domain of murine T cell intracellular antigen-1 (TIA-1) and its RNA recognition mode. (2008)
  • Author(s): Kuwasako K., Takahashi M., Tochio N., Abe C., Tsuda K., Inoue M., Terada T., Shirouzu M., Kobayashi N., Kigawa T., Taguchi S., Tanaka A., Hayashizaki Y., Guntert P., Muto Y., Yokoyama S.
  • Journal Title: Biochemistry. 47 Pages: 64-64
  • Peer Reviewed
• [Journal Article] Crystal structure of archaeal tRNA (m1G37) methyltransferase aTrm5 (2008)
  • Author(s): Goto-Ito S., Ito T., Ishii R., Muto Y., Bessho Y., Yokoyama S.
  • Journal Title: Proteins 72 Pages: 1274-1289
  • Peer Reviewed
• [Journal Article] Complex assembly mechanism and an RNA-bindig mode of the human p1-SF3b155 spliceosomal protein complex identified by NMR solution structure and functional analyses. (2008)
  • Author(s): Kuwasako K., Dohmae N., Inoue M., Shirouzu M., Taguchi S., Guntert P., Seraphin B., Muto Y., Yokoyama S.
  • Journal Title: Proteins 71 Pages: 1617-1636
  • Peer Reviewed
• [Journal Article] Complex assembly mechanism and an RNA-binding mode of the human p14-SF3b155 spliceosomal protein complex identified by NMR solution structure and functional analyses (2008)
  • Author(s): Kuwasako K., et al.
  • Journal Title: Proteins 71 Pages: 1617-1636
  • Peer Reviewed
• [Journal Article] Crystal structure of archaeal tRNA(m1G37)methyltransferase aTrm5 (2008)
  • Author(s): Goto-Ito S., et al
  • Journal Title: Proteins 72 Pages: 1274-1289
  • Peer Reviewed
• [Journal Article] Solution structure of the second RNA recognition motif (RRM) domain of murine T cell intracellular antigen-1 (TIA-1) and its RNA recognition mode (2008)
  • Author(s): Kuwasako K, Takahashi, M, et al.
  • Journal Title: Biochemistry 47 Pages: 6437-6450
  • Peer Reviewed
• [Journal Article] The RRM domain of poly (A)-specific ribonuclease has a noncanonical binding site for mRNA cap analog recognition (2008)
  • Author(s): Nagata T., et al.
  • Journal Title: Nucleic Acid Research 36 Pages: 4754-4767
  • Peer Reviewed
• [Journal Article]
• [Presentation] RNAの高次構造に依存したhTra2-βのRNA認識メカニズムの解明 (2010)
  • Author(s): 津田健吾、桑迫香奈子、高橋真梨、染谷龍彦、白水美香子、寺田貴帆、井上真、木川隆則、菅野純夫、横山茂之、武藤裕
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会(BMB2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] Solution Structure of Splicing Factor Motif (SFM) in Prp18 from Homo sapiens (2010)
  • 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.
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会(BMB2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] Structural basis for the sequence-specific RNA-recognition mechanism of Bruno-like family proteins (2010)
  • Author(s): Muto Y.
  • Organizer: The 19th CDB Meeting : RNA Sciences in Cell and Developmental Biolgy
  • Place of Presentation: Kobe
  • Year and Date: 2010-05-10
• [Presentation] Structural basis for the sequence-specific RNA-recognition mechanism of Bruno-like family proteins (2010)
  • Author(s): Muto, Y.
  • Organizer: The 19th CDB Meeting : RNA Sciences in Cell and Developmental Biology
  • Place of Presentation: Kobe
  • Year and Date: 2010-05-10
• [Presentation] AU-rich RNA-binding induces changes in the quaternary structure of AUH (2009)
  • Author(s): 栗本一基、桑迫香奈子、Alan M.Sandercock,雲財悟、Carol V.Robinson,武藤裕、横山茂之
  • Organizer: 2009年度日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] eIF4BとeIF4HのRNAに対する結合能の違い (2009)
  • Author(s): 津田健吾、鈴木咲良、桑迫香奈子、井上真、白水美香子、寺田貴帆、木川隆則、武藤裕、菅野純夫、横山茂之
  • Organizer: 2009年度日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] miRNAの抑制に関わる蛋白質の構造解析 (2009)
  • Author(s): 高橋真梨、染谷龍彦、井上真、寺田貴帆、白水美香子、渡部暁、原田拓志、桑迫香奈子、津田健吾、河合剛太、坂本泰一、木川隆則、菅野純夫、武藤裕、横山茂之
  • Organizer: 2009年度日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] Structural and functional characterization of the NHR1 domain of the Drosophila Neuralized E3 ligase in the Notch signaling pathway (2009)
  • Author(s): 何発虎、斎藤講平、小林直宏、原田拓志、渡部暁、木川隆則、Peter Guntert,小原収、田仲昭子、雲財悟、武藤裕、横山茂之
  • Organizer: 2009年度日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] RNAi関連因子hTRABP2の構造生物学的解析 (2009)
  • Author(s): 山下征輔、川添将仁、竹本千重、赤坂領吾、永田崇、武藤裕、木川隆則、滝元宏治、脇山素明、横山茂之
  • Organizer: 2009年度日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] AU-rich RNA-binding induces changes in the quaternary structure of AUH (2009)
  • Author(s): 桑迫香奈子
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Structural and functional characterization of the NHR1 domain of the Drosophila Neuralized E3 ligase in the Notch signaling pathway (2009)
  • Author(s): He, F.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] eIF4BとeIF4HのRNAに対する結合能の違い (2009)
  • Author(s): 津田健吾
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] miRNAの抑制に関わるタンパク質の構造解析 (2009)
  • Author(s): 高橋真梨
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Characterization of RNA aptamers against SRP19 protein having sequences different from SRP RNA (2009)
  • Author(s): Haraguchi, Y.
  • Organizer: The 6th International symposium on Nucleic Acid Chemistry
  • Place of Presentation: Gifu
  • Year and Date: 2009-09-27
• [Presentation] 構造生物学的研究によって明らかにされる"RNA recognition motif (RRM)"の多様性 (2009)
  • Author(s): 桑迫香奈子、菅野純夫、林崎良英、木川隆則、武藤裕、横山茂之
  • Organizer: RNAフロンティアミーティング2009
  • Place of Presentation: 葉山
  • Year and Date: 2009-09-26
• [Presentation] 構造生物学的研究によって明らかにされる"RNA recognition motif(RRM)"の多様性 (2009)
  • Author(s): 桑迫香奈子
  • Organizer: RNAフロンティアミーティング2009
  • Place of Presentation: 葉山
• [Presentation] PARNのRRMドメインによるmRNA 5'キャップの認識機構 (2008)
  • Author(s): 永田崇, et al.
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-11
• [Presentation] RNA recognition motifドメインにおける分子認識の違い (2008)
  • Author(s): 津田健吾、桑迫香奈子、高橋真梨、染谷龍彦、武藤裕、白水美香子、寺田貴帆、井上真、木川隆則、菅野純夫、横山茂之
  • Organizer: 2008年度日本分子生物学会・生化学会 合同大会
  • Year and Date: 2008-12-09
• [Presentation] MBNL2蛋白質に見られるCCCH-type Zn fingerドメインの新規溶液構造 (2008)
  • Author(s): 何発虎、党偉栄、阿部千景、津田健吾、井上真、木川隆則、松田貴意、矢吹孝、青木雅昭、関英子、寺田貴帆、白水美香子、田仲昭子、菅野純夫、武藤裕、横山茂之
  • Organizer: 2008年度日本分子生物学会・生化学会 合同大会
  • Year and Date: 2008-12-09
• [Presentation] 選択的スプライシングを調節するTIA-1 RRM2の立体構造解析およびRNA認識 (2008)
  • Author(s): 高橋真梨、桑迫香奈子、栃尾尚哉、阿部千景、津田健吾、井上 真、寺田貴帆、白水美香子、小林直宏、木川隆則、田口精一、田仲昭子、林崎良英、Peter Guntert,武藤裕、横山茂之
  • Organizer: 2008年度日本分子生物学会・生化学会 合同大会
  • Year and Date: 2008-12-09
• [Presentation] Complex assembly mechanism and an RNA-binding mode of the human p14-SF3b155 spliceosomal protein complex identified by NMR solution structure and functional analysis (2008)
  • Author(s): Kanako Kuwasako, Naoshi Dhomae, Mio Inoue, Mikako Shirouzu, Seiichi Taguchi, Peter Guntert, Bertrand Seraphin, Yutaka Muto, Shigeyuki Yokoyama
  • Organizer: 2008年度日本分子生物学会・生化学会 合同大会
  • Year and Date: 2008-12-09
• [Presentation] RNA recognition motif ドメインにおける分子認識の違い (2008)
  • Author(s): 津田健吾, et al.
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-09
• [Presentation] MBNL2蛋白質に見られるCCCH-type Zn finger ドメインの新規溶液構造 (2008)
  • Author(s): He, et al.
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-09
• [Presentation] 選択的スプライシングを調節するTIA-1RRM2の立体構造解析およびRNAの認識 (2008)
  • Author(s): 高橋真梨, et al.
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-09
• [Presentation] Complex assembly mechanism and an RNA-binding mode of the human p14-SH3b155 spliceosomal protein complex identified by NMR solution structure and functional analysis (2008)
  • Author(s): 桑迫香奈子, et al.
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-09
• [Presentation] Structural Studies of the RRM : mRNA 5' cap complex (2008)
  • Author(s): Nagata T., Suzuki S., Endo R., Shirouzu M., Terada T., Inoue M., Kigawa T., Guntert P., Hayashizaki Y., Muto Y., Yokoyama S.
  • Organizer: XXIII International Conference on Magnetic Resonance in Biological Systems
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-08-28
• [Book] 生体の科学(59巻5号 分子遺伝学・遺伝子・遺伝子工学 miRNA) (2008)
  • Author(s): 武藤裕