Molecular basis for the formation of translational repression complex that regulates stem cell differentiation

• Project/Area Number: 20570111
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Yokohama City University
• Principal Investigator: NAGATA Takashi Yokohama City University, 生命ナノシステム科学研究科, 助教 (10415250)
• Co-Investigator(Kenkyū-buntansha): KATAHIRA Masato 京都大学, エネルギー理工学研究所, 教授 (70211844)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: Musashi / 翻訳抑制 / 幹細胞 / 分化制御 / RNA結合タンパク質 / NMR / RBD / 溶液構造 / 神経幹細胞

Research Abstract

Musashi1 (Msi1) is a neural protein that suppresses translation of target mRNAs and contributes in maintenance of cell stemness and tumorigenesis. We have determined the RNA recognition mechanism by Msi1. Minimal RNA sequence for Msi1, and the binding mechanism of Msi1 that we have elucidated would provide important clues to discover new target genes for Msi1. Meanwhile, we have determined the structure of PABP and identified its Msi1 binding sites. Finally, we have prepared a protocol for building protein and nucleic acid complex models that would support the structural analysis of translational repression complex.

Research Products

• [Journal Article] Structures of the first and second double-stranded RNA-binding domains of human TAR RNA-binding protein (2011)
  • Author(s): Nagata, T., Yokohama, S., 他(12人中2番目、永田は1番目の著者と同じ貢献)
  • Journal Title: Protein Sci 20 Pages: 118-130
  • Peer Reviewed
• [Journal Article] Solution structures of the trihelix DNA-binding domains of the wild-type and a phosphomimetic mutant of Arabidopsis GT-1: mechanism for an increase in DNA-binding affinity through phosphorylation. (2010)
  • Author(s): Nagata, T., Katahira, M., 他(9人中1番目)
  • Journal Title: Proteins 78 Pages: 3033-3047
  • Peer Reviewed
• [Journal Article] Solution structures of the trihelix DNA-binding domains of the wild-type and a phosphomimetic mutant of Arabidopsis GT-1 : Mechanism for an increase in DNA-binding affinity through phosphorylation (2010)
  • Author(s): Nagata, T., Katahira, M., et al.
  • Journal Title: PROTEINS Volume: 78 Pages: 3033-3047
  • Peer Reviewed
• [Journal Article] Structures of the first and second double-stranded RNA-binding domains of human TAR RNA-binding protein (2010)
  • Author(s): Yamashita, S., Nagata, T., et al
  • Journal Title: Protein Sci. Volume: 20 Pages: 118-130
  • Peer Reviewed
• [Journal Article] Solution structures of the trihelix DNA-binding domains of the wild-type and a phosphomimetic mutant of Arabidopsis GT-1, implying a mechanism for an increase in DNA-binding affinity through phosphorylation (2010)
  • Author(s): Nagata, T.
  • Journal Title: Proteins (in press)
  • Peer Reviewed
• [Journal Article] Structure, interaction, and real-time monitoring of the enzymatic reaction of wild-type APOBEC3G (2009)
  • Author(s): Nagata, T., Katahira, M., 他(10人中2番目)
  • Journal Title: EMBO J. 28 Pages: 440-451
  • Peer Reviewed
• [Journal Article] Unusual thermal disassembly of the SPFH domain oligomer from Pyrococcus horikoshii (2009)
  • Author(s): Nagata, T., Hiroaki, H., 他(9人中3番目)
  • Journal Title: Bionhys.J 97 Pages: 2034-2043
  • Peer Reviewed
• [Journal Article] Structure and real-time monitoring of the enzymatic reaction of APOBEC3G which is involved in anti-HIV activity (2009)
  • Author(s): Nagata, T., Katahira, M., 他(10人中2番目)
  • Journal Title: Nucleic Acids Symp Ser 53 Pages: 87-88
  • Peer Reviewed
• [Journal Article] Structure, interaction, and real-time monitoring of the enzymatic reaction of wild-type APOBEC3G (2009)
  • Author(s): Furukawa, A.
  • Journal Title: EMBO J. 28 Pages: 440-451
  • Peer Reviewed
• [Journal Article] Unusual thermal disassembly of the SPFH domain oligomer from Pyrococcus horikoshii (2009)
  • Author(s): Kuwahara, Y.
  • Journal Title: Biophys J. 97 Pages: 2034-2043
  • Peer Reviewed
• [Journal Article] Structure and real-time monitoring of the enzymatic reaction of APOBEC3G which is involved in anti-HIV activity (2009)
  • Author(s): Furukawa, A.
  • Journal Title: Nucleic Acids Symp Ser. 53 Pages: 87-88
  • Peer Reviewed
• [Journal Article] Structure, interaction, and real-time monitoring of the enzymatic reaction of wild-type APO (2009)
  • Author(s): Ayako Furukawa
  • Journal Title: European Molecular Biology Organization's journal (EMBO J) 28 Pages: 440-451
  • 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., Yokohama, S., 他(13人中1番目)
  • Journal Title: Nucleic Acids Res 36 Pages: 4754-4767
  • Peer Reviewed
• [Journal Article] Elucidation of the mode of interaction in the UP1-telomerase RNA-telomeric DNA ternary complex which serves to recruit telomerase to telomeric DNA and to enhance the telomerase activity (2008)
  • Author(s): Nagata, T., Katahira, M., 他(13人中1番目)
  • Journal Title: Nucleic Acids Res 36 Pages: 6816-6824
  • Peer Reviewed
• [Journal Article] N- and C-terminal Fragments of a Globular Protein Constructed by Elongation of Modules as a Units Associated for Functional Complementation (2008)
  • Author(s): Tsuji, T., Nagata, T., Yanagawa, H.
  • Journal Title: J. Biochem 144 Pages: 513-521
  • NAID: 10024912926
  • Peer Reviewed
• [Journal Article] Structural analysis of Musashi-RNA complex on the basis of long-range structural information (2008)
  • Author(s): Nagata, T., Katahira, M., 他(10人中9番目)
  • Journal Title: Nucleic Acids Symp. Ser 52 Pages: 193-194
  • Peer Reviewed
• [Journal Article] NMR assignments and the identification of the secondary structure of the anti-retroviral cytidine deaminase (2008)
  • Author(s): Nagata, T., Katahira, M., 他(8人中2番目)
  • Journal Title: Nucleic Acids Symp. Ser 52 Pages: 183-184
  • Peer Reviewed
• [Journal Article] Elucidation of the mode of interaction in the UP1-telomerase RNA-telomeric DNA ternary complex which serves to recruit telomerase to telomeric DNA and to enhance the telomerase activity (2008)
  • Author(s): Takashi Nagata
  • Journal Title: Nucleic Acids Research 36 Pages: 6816-6824
  • Peer Reviewed
• [Journal Article] Structural analysis of Musashi-RNA complex on the basis of long-range structural informat (2008)
  • Author(s): Takako Ohyama
  • Journal Title: Nucleic Acids Symposium Series 52 Pages: 193-194
  • Peer Reviewed
• [Journal Article] NMR assignments and the identification of the secondary structure of the anti-retroviral cytidine deaminase (2008)
  • Author(s): Ayako Furukawa
  • Journal Title: Nucleic Acids Symposium Series 52 Pages: 183-184
  • Peer Reviewed
• [Presentation] The real-time monitoring of the enzymatic reaction of an anti-HIV factor APOBEC3G (2010)
  • Author(s): Furukawa, A.
  • Organizer: Korea-Japan Bilateral NMR Symposium
  • Place of Presentation: 韓国、ソウル
  • Year and Date: 2010-11-25
• [Presentation] A mechanism for an increase in DNA-binding affinity of the trihelix DNA-binding domain via its phosphorylation (2010)
  • Author(s): Nagata, T.
  • Organizer: The 37th International Symposium on Nucleic Acids Chemistry 2010
  • Place of Presentation: 横浜
  • Year and Date: 2010-11-10
• [Presentation] Real-time monitoring of the enzymatic reaction of APOBEC3G possessing anti-HIV activity, and the structure and interaction of the RNA aptamer against prion protein (2010)
  • Author(s): Furukawa, A.
  • Organizer: The 10th KIAS Conference on Protein Structure and Function
  • Place of Presentation: 韓国、ソウル
  • Year and Date: 2010-09-30
• [Presentation] Real-time monitoring of the enzymatic reaction of APOBEC3G possessing anti-HIV activity, and the structure of the RNA aptamer against prion protein (2010)
  • Author(s): Furukawa, A., Nagata, T., Katahira, M., et al.
  • Organizer: International Symposium of Korean Society of Biochemistry and Molecular Biology-Structural Biology and Drug Discovery
  • Place of Presentation: 韓国、チェジュ島
  • Year and Date: 2010-08-27
• [Presentation] The real-time monitoringof the enzymatic reaction of an anti-HIV factor APOBEC3G (2010)
  • Author(s): Furukawa, A.
  • Organizer: XXIV International Conference on Magnetic Resonance in Biological Systems
  • Place of Presentation: オーストラリア、ケアンズ
  • Year and Date: 2010-08-25
• [Presentation] Real-time monitoring of the enzymatic reaction of APOBEC3G possessing anti-HIV activity, and the structure of the RNA aptamer against prion protein (2010)
  • Author(s): Furukawa, A.
  • Organizer: International Symposium of Korean Society of Biochemistry and Molecular Biology -Structural Biology and Drug Discovery-
  • Place of Presentation: 韓国、チェジュ島
  • Year and Date: 2010-08-25
• [Presentation] Real-time monitoring of the enzymatic reaction of APOBEC3G possessing anti-HIV activity, and the structure and interaction of the RNA aptamer against prion protein (2010)
  • Author(s): Katahira, M.
  • Organizer: XXIV International Conference on Magnetic Resonance in Biological Systems
  • Place of Presentation: オーストラリア、ケアンズ
  • Year and Date: 2010-08-23
• [Presentation] The real-time monitoring of the enzymatic reaction of an anti-HIV factor APOBEC3G (2010)
  • Author(s): Furukawa, A., Nagata, T., Katahira, M., et al.
  • Organizer: XXIV International Conference on Magnetic Resonance in Biological Systems
  • Place of Presentation: オーストラリア、ケアンズ
• [Presentation] Real-time monitoring of the enzymatic reaction of APOBEC3G possessing anti-HIV activity, and the structure and interaction of the RNA aptamer against prion protein (2010)
  • Author(s): Mashima, T., Nagata, T., Katahira, M., et al.
  • Organizer: XXIV International Conference on Magnetic Resonance in Biological Systems
  • Place of Presentation: オーストラリア、ケアンズ(招待講演)
• [Presentation] Real-time monitoring of the enzymatic reaction of APOBEC3G possessing anti-HIV activity, and the structure and interaction of the RNA aptamer against prion protein (2010)
  • Author(s): Furukawa, A., Nagata, T., Katahira, M., et al.
  • Organizer: The 10th KIAS Conference on Protein Structureand Function
  • Place of Presentation: 韓国、ソウル(招待講演)
• [Presentation] The real-time monitoringof the enzymatic reaction of an anti-HIV factor APOBEC3G (2010)
  • Author(s): Furukawa, A., Nagata, T., Katahira, M., et al.
  • Organizer: Korea-Japan Bilateral Symposium
  • Place of Presentation: 韓国、ソウル
• [Presentation] Molecular Mechanism for an increase in DNA-binding affinity of plant transcription factor GT-1 through phosphorylation (2010)
  • Author(s): 永田崇、片平正人, 他
  • Organizer: 第10回日本蛋白質科学会年会
  • Place of Presentation: 札幌
• [Presentation] HIV遺伝子上でのAPOBEC3Gによるシチジンデアミネーション反応の動作機序 (2010)
  • Author(s): 古川亜矢子、永田崇、片平正人, 他
  • Organizer: 第10回日本蛋白質科学会年会
  • Place of Presentation: 札幌
• [Presentation] 分化制御の鍵をにぎる翻訳抑制複合体のNMR構造機能解析 (2010)
  • Author(s): 大山貴子、永田崇、片平正人, 他
  • Organizer: 第12回日本RNA学会年会
  • Place of Presentation: 東京
• [Presentation] The real-time monitoring of the enzymatic reaction of an anti-HIV factor APOBEC3G (2010)
  • Author(s): 古川亜矢子、永田崇、片平正人, 他
  • Organizer: 第48回生物物理学会
  • Place of Presentation: 仙台
• [Presentation] NMRシグナルを用いた抗ウィルス因子活性のリアルタイムモニタリング (2010)
  • Author(s): 古川亜矢子、永田崇、片平正人, 他
  • Organizer: 第58回日本ウィルス学会学術集会
  • Place of Presentation: 徳島
• [Presentation] Musashi1蛋白質-標的RNA複合体に含まれる新たな核酸塩基認識機構 (2010)
  • Author(s): 大山貴子、永田崇、片平正人, 他
  • Organizer: 第49回NMR討論会
  • Place of Presentation: 東京
• [Presentation] RNAアプタマー:プリオンタンパク質部分ペプチド複合体の構造及びA3Gタンパク質のDNA上スライディングの解析 (2010)
  • Author(s): 古川亜矢子、永田崇、片平正人, 他
  • Organizer: 第49回NMR討論会
  • Place of Presentation: 東京
• [Presentation] APOBEC3Gが抗HIV活性を発揮する酵素反応のリアルタイムモニタリング (2010)
  • Author(s): 古川亜矢子、永田崇、片平正人, 他
  • Organizer: 平成22年度日本分光学会
  • Place of Presentation: 京都
• [Presentation] Structural and functional analysis of the translational repression complex that plays a key role in differentiation regulation (2010)
  • Author(s): Ohyama, T., Nagata, T., Katahira, M., 他
  • 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
  • Place of Presentation: 神戸
• [Presentation] 植物転写因子GT-1がリン酸化によりDNA結合能を上昇させる分子機構の解明 (2010)
  • Author(s): 藤本なつき・永田崇・片平正人, 他
  • 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
  • Place of Presentation: 神戸
• [Presentation] RNAi関連因子TRBPの構造生物学的解析 (2010)
  • Author(s): 山下征輔、永田崇, 他
  • 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
  • Place of Presentation: 神戸
• [Presentation] Real-time monitoring of the enzymatic reaction of APOPBEC3G possessing anti-HIV activity, and the structure of the RNA aptamer against prion (2009)
  • Author(s): Katahira, M.
  • Organizer: The 3rd Asia-Pacific NMR Symposium
  • Place of Presentation: 韓国、済州島
  • Year and Date: 2009-10-25
• [Presentation] Structure and real-time monitoring of the enzymatic reaction of APOBEC3G which is involved in anti-HIV activity (2009)
  • Author(s): Furukawa, A.
  • Organizer: The 3rd Asia-Pacific NMR Symposium
  • Place of Presentation: 韓国、済州島
  • Year and Date: 2009-10-25
• [Presentation] Structure and real-time monitoring of the enzymatic reaction of APOBEC3G which is involved in anti-HIV activity (2009)
  • Author(s): 古川亜矢子
  • Organizer: The 3rd Asia-Pacific NMRSymposium
  • Place of Presentation: 韓国、済州島
• [Presentation] Structure and real-time monitoring of the enzymatic reaction of APOBEC3G which is involved in anti-HIV activity (2009)
  • Author(s): 古川亜矢子
  • Organizer: 第6回国際核酸化学シンポジウム
  • Place of Presentation: 高山
• [Presentation] Molecular Mechanism for the reinforcement of DNA-binding activity of GT-1 via phosphorylation (2009)
  • Author(s): 永田崇
  • Organizer: 第9回日本蛋白質科学会年会
  • Place of Presentation: 熊本
• [Presentation] HIVの複製を阻害するタンパク質APOBEC3Gの構造、相互作用及び酵素反応のリアルタイムモニタリング (2009)
  • Author(s): 古川亜矢子
  • Organizer: 第9回日本蛋白質科学会年会
  • Place of Presentation: 熊本
• [Presentation] 熱により不可逆的に解離するPH0470由のSPFHドメイン多量体 (2009)
  • Author(s): 桑原陽太
  • Organizer: 第9回日本蛋白質科学会年会
  • Place of Presentation: 熊本
• [Presentation] 抗HIV活性を有する天然型APOBEC3Gタンパク質の構造、1本鎖DNAとの相互作用及び酵素反応のリアルタイムモニタリング (2009)
  • Author(s): 古川亜矢子
  • Organizer: 第47回生物物理学会
  • Place of Presentation: 徳島
• [Presentation] RNAi関連因子hTRBP2の構造生物学的解析""Structural analysis of hTRBP2 (2009)
  • Author(s): 山下征輔
  • Organizer: 第32回分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 抗HIV活性を保持するタンパク質APOBEC3Gの酵素反応のリアルタイムモニタリング (2009)
  • Author(s): 古川亜矢子
  • Organizer: 第32回分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 翻訳制御に関わるMusashi1とPABP1の相互作用と立体構造の解析 (2009)
  • Author(s): 飯倉裕之
  • Organizer: 第32回分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 植物遺伝子の光制御に関連したGT-1タンパク質の構造と相互作用の研究""Structural and DNA binding analyses of GT-1 involved in the photoregulation of plant genes (2009)
  • Author(s): 藤本なつき
  • Organizer: 第32回分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Structural Studies of the RRM:mRNA 5' cap complex (2008)
  • Author(s): Nagata, T.
  • Organizer: XXIII International Conference on Magnetic Resonance in Biological Systems
  • Place of Presentation: 米国、サンディエゴ
  • Year and Date: 2008-08-28
• [Presentation] Structures and interactions of 4'-thioDNA and RNA/DNA-binding proteins (2008)
  • Author(s): Katahira, M.
  • Organizer: XXIII International Conference on Magnetic Resonance in Biological Systems
  • Place of Presentation: 米国、サンディエゴ
  • Year and Date: 2008-08-26
• [Presentation] Structural analyis of Musashi-RNA complex with paramagnetic effects (2008)
  • Author(s): Ohyama, T.
  • Organizer: XXIII International Conference on Magnetic Resonance in Biological Systems
  • Place of Presentation: 米国、サンディエゴ
  • Year and Date: 2008-08-26
• [Presentation] Structure determination of a multi-domain protein by the use of PRE and RDC, and the unexpected A-form structure of 4'-thioDNA exhibiting nuclease-resistance (2008)
  • Author(s): Katahira, M.
  • Organizer: Korea-Japan Symposium on Biological NMR
  • Place of Presentation: 韓国、ソウル
  • Year and Date: 2008-04-25
• [Presentation] Structural analyis of Musashi-RNA complex with paramagnetic effects (2008)
  • Author(s): Takako Ohyama
  • Organizer: 23rd International Conference of Magnetic Resonance in Biological Systems.
  • Place of Presentation: 米国、San Diego
• [Presentation] Structural Studies of the RRM : mRNA 5' cap complex (2008)
  • Author(s): Takashi Nagata
  • Organizer: 23rd International Conference of Magnetic Resonance in Biological Systems.
  • Place of Presentation: 米国、San Diego
• [Presentation] Structures and interactions of 4'-thioDNA and RNA/DNA-binding proteins (2008)
  • Author(s): Takako Ohyama
  • Organizer: 23rd International Conference of Magnetic Resonance in Biological Systems.
  • Place of Presentation: 米国、San Diego
• [Presentation] ロングレンジの距離情報の抽出に基づいたマルチドメインタンパク質Musashiと標的RNAの複合体の構造解析 (2008)
  • Author(s): 大山貴子
  • Organizer: RNA meeting 2008
  • Place of Presentation: 札幌
• [Presentation] NMR assignments and the identification of the secondary structure of the anti-retroviral cytidine deaminase (2008)
  • Author(s): Ayako Furukawa
  • Organizer: Joint Symposium of 18th International Roundtable on Nucleosides, Nucleotides and Nucleic Acids and 35th International Symposium on Nucleic Acids Chemistry.
  • Place of Presentation: 京都
• [Presentation] Hsp70のHIV-1感染抑制 (2008)
  • Author(s): 杉山隆一
  • Organizer: 第56回ウィルス学会
  • Place of Presentation: 岡山
• [Presentation] A simultaneous RNA-binding mode of two RNA-binding domains of Musashi-1 analyzed by paramagnetic effects, PRE, PCS, and RDC (2008)
  • Author(s): Takashi Nagata
  • Organizer: 第46回日本生物物理学会
  • Place of Presentation: 福岡
• [Presentation] Musashiタンパク質とPABPの相互作用の解析 (2008)
  • Author(s): 樋口敬介
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会・合同大会
  • Place of Presentation: 神戸
• [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
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会・合同大会
  • Place of Presentation: 神戸
• [Presentation] HIVの複製を阻害するタンパク質APOBEC3Gの構造と相互作用の解析 (2008)
  • Author(s): 古川亜矢子
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会・合同大会
  • Place of Presentation: 神戸
• [Presentation] 植物遺伝子の光制御に関連したGT-1タンパク質の構造と相互作用の研究 (2008)
  • Author(s): 長崎祐也
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会・合同大会
  • Place of Presentation: 神戸
• [Presentation] テロメレースのリクルート及び活性の増強をもたらすUP1-テロメアDNA-テロメアRNAの三者複合体の相互作用の解明 (2008)
  • Author(s): 藤本なつき
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会・合同大会
  • Place of Presentation: 神戸
• [Remarks]
  • URL: http://www.yokohama-cu.ac.jp/res/researcher/info/090401katahira.html
• [Patent(Industrial Property Rights)] Hsp70を有効成分として含有するHIV-1感染症治療剤 (2010)
  • Inventor(s): 高久洋、杉山隆一、片平正人、永田崇、古川亜矢子
  • Industrial Property Rights Holder: 千葉工業大学
  • Industrial Property Number: 2010-067254
  • Filing Date: 2010-03-24