ｍｉｃｒｏＲＮＡが関与する翻訳抑制機構の素過程の解析

• Project Area: Functional machinery for non-coding RNAs
• Project/Area Number: 24115715
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Nagoya City University (2013); Microbial Chemistry Research Foundation (2012)
• Principal Investigator: 藤原 俊伸 名古屋市立大学, 薬学研究科(研究院), 教授 (80362804)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000); Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: microRNA / 翻訳制御 / miRNA

Research Abstract

cap構造の認識から開始される翻訳開始複合体の形成は翻訳の律速段階であり、タンパク質合成を調節するうえでこの過程を制御することは効率がよく、翻訳開始因子群のリン酸化を担うシグナル伝達因子を中心に実例も数多くある。そしてこれまでにmiRNAによる翻訳抑制の標的は翻訳の律速段階である開始であることが強く示唆されている。したがって翻訳を下方修正する手段としてmiRNAによる翻訳開始の抑制は効率的であるといえる。しかしながら、高等真核生物におけるmiRNAによる翻訳開始過程の抑制の素過程は、精力的に研究されているmiRNA が触媒するmRNAの分解過程とは異なりその詳細が明らかにされていない。そこで、miRNAによる翻訳開始抑制時に、翻訳開始過程のどのステップが標的とされているのか、またどのような因子を標的としているのかを申請者が有する生化学的技法を駆使して、明らかにすることを試みた。
その結果、miRNAによる翻訳抑制機構は、翻訳開始因子の1つを標的としていることを明らかにした。

Current Status of Research Progress

Reason

25年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

25年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Structural insights into the recruitment of SMRT by the corepressor SHARP under phosphorylative regulation. (2014)
  • Author(s): Mikami S, Kanaba T, Takizawa N, Kobayashi A, Maesaki R, Fujiwara T, Ito Y,Mishima M.
  • Journal Title: Structure. Volume: 22 Issue: 1 Pages: 35-46
  • DOI: 10.1016/j.str.2013.10.007
  • Peer Reviewed
• [Journal Article] The essential role for the RNA triphosphatase Cetlp in nuclear import of the mRNA capping enzyme Cetlp-Ceglp complex of Saccharomyces cerevisiae (2013)
  • Author(s): Naoki Takizawa, Toshinobu Fujiwara, Manabu Yamasaki, Ayako Saito, Akira Fukao, Akio Nomoto, Kiyobisa Mizumoto
  • Journal Title: ProsOne Volume: 8(10) Issue: 10 Pages: e78000-e78000
  • DOI: 10.1371/journal.pone.0078000
  • Peer Reviewed
• [Journal Article] Microbial fluorescence sensing for human neurotensin receptor type lusing Ga-engineered yeast cells (2013)
  • Author(s): Jun Ishii, Asami Oda, Shota Togawa, Akira Fukao, Toshinobu Fujiwara, Chiaki Ogino and Akihiko Kondo
  • Journal Title: Analytical Biochemistry Volume: 446 Pages: 37-43
  • DOI: 10.1016/j.ab.2013.10.016
  • Peer Reviewed
• [Journal Article] Targeting cancer cell-specific RNA interference by siRNA delivery using a complex carrier of affibody-displaying bio-nanocapsules and liposomes. (2013)
  • Author(s): Nishimura Y, Mieda H, Ishii J, Ogino C, Fujiwara T, Kondo A.
  • Journal Title: J Nanobiotechnology. Volume: 11 Issue: 1 Pages: 19-19
  • DOI: 10.1186/1477-3155-11-19
  • Peer Reviewed
• [Journal Article] Structure of the second RRM domain of Nrd1, a fission yeast MAPK target RNA binding protein, and implication for its RNA recognition and regulation. (2013)
  • Author(s): Kobayashi A, Kanaba T, Satoh R, Fujiwara T, Ito Y, Sugiura R, Mishima M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 437 Issue: 1 Pages: 12-17
  • DOI: 10.1016/j.bbrc.2013.06.008
  • Peer Reviewed
• [Journal Article] Staphylococcal superantigen-like protein 10 (SSL10) inhibits blood coagulation by binding to prothrombin and factor Xa via theirγ-carboxyglutamic acid (Gla) domain (2013)
  • Author(s): Itoh S, Yokoyama R, Kamoshida G, Fujiwara T, Okada H, Takii T, Tsuji T, Fujii S, Hashizume H, Onozaki K
  • Journal Title: J Biol Chem Volume: 288 Issue: 30 Pages: 21569-21580
  • DOI: 10.1074/jbc.m113.451419
  • Peer Reviewed
• [Journal Article] Double PHD finger proteins DPF3a and 3b are reouired as transcriptional coactivators in the SWI/SNF complex-dependent activation of the NF-κB Re1A/p50 heterodimer (2012)
  • Author(s): Ishizaka A, Mizutani T, Kobayashi K, Tando T, Sakurai K, Fujiwara T, Iba H
  • Journal Title: The Journal of Biological Chemistry Volume: (印刷中) Issue: 15 Pages: 11924-11933
  • DOI: 10.1074/jbc.m111.322792
  • Peer Reviewed
• [Journal Article] Translational inhibition by deadenylation-independent mechanismsis central to microRNA-mediated silencing in zebrafish (2012)
  • Author(s): Yuichiro Mishima
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 109(4) Issue: 4 Pages: 1104-1109
  • DOI: 10.1073/pnas.1113350109
  • Peer Reviewed
• [Journal Article] Functional and direct interaction between the RNA binding protein HuD and active Akt1 (2012)
  • Author(s): Toshinobu Fujiwara
  • Journal Title: Nucleic Acids Research Volume: 40(5) Issue: 5 Pages: 1944-1953
  • DOI: 10.1093/nar/gkr979
  • Peer Reviewed
• [Presentation] Analyses of cell type specific translation from the IRES mRNA derived from two different Poliovirus strains (2014)
  • Author(s): 貞廣暁利、藤原俊伸
  • Organizer: 第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
  • Place of Presentation: 長野
• [Presentation] Translational regulation by HuD through the interaction with eIF3 (2014)
  • Author(s): 高辻良文、藤原俊伸
  • Organizer: 第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
  • Place of Presentation: 長野
• [Presentation] Effect of eIF4B phosphorylation by active Akt1 recruited into cap binding complex by HuD on translation (2014)
  • Author(s): 矢野雄暉、藤原俊伸
  • Organizer: 第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
  • Place of Presentation: 長野
• [Presentation] Functional relationship between HuD and Paip2 in differentiation of PC12 cells (2014)
  • Author(s): 大塚衆志、藤原俊伸
  • Organizer: 第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
  • Place of Presentation: 長野
• [Presentation] Dissecting roles of Paip1 in HuD mediated translation activation (2014)
  • Author(s): 青山智彦、藤原俊伸
  • Organizer: 第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
  • Place of Presentation: 長野
• [Presentation] Novel cell free translation system using human cultured cell lines (2014)
  • Author(s): 深尾亜喜良、藤原俊伸
  • Organizer: 第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
  • Place of Presentation: 長野
• [Presentation] High-throughput screening approach combining siRNA reverse-transfection and reporter mRNA transfection (2014)
  • Author(s): 藤原俊伸
  • Organizer: 第 8 回 「 長野ミーティング :生物資源の有効利用を目指して」
  • Place of Presentation: 長野
• [Presentation] HuD accelerates cap-dependent translation through eIF4B phosphorylation by active Akt1. (2013)
  • Author(s): Toshinobu Fujiwara
  • Organizer: The 2nd Meeting on RNA and Biofunctions-Asia Study "RNA Biofunctions and Viruses"
  • Place of Presentation: Hotel Leopalace Hakata （福岡）
  • Year and Date: 2013-01-10
• [Presentation] The mechanism of translational control which targets a translation initiation complex (2013)
  • Author(s): Akira Fukao, Nahum Sonenberg, Christian Thoma and Toshinobu Fujiwara
  • Organizer: 2013 RiboClub Annual Meeting
  • Place of Presentation: ケベック
• [Presentation] The RNA-binding protein HuD regulates cap-dependent translation by binding to the mRNA nuclear export receptor TAP/NXF1 (2013)
  • Author(s): Ryosuke Satoh, Akira Fukao, Akio Nomoto and Toshinobu Fujiwara
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] HuD accelerates cap-dependent translation through eIF4B phosphorylation by active Akt1 (2013)
  • Author(s): Yuki Yano, Akira Fukao and Toshinobu Fujiwara
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Analyses of underlying relationship between the subcellular localization and stimulatory activity on cap-dependent translation of RNA-binding protein HuD. (2012)
  • Author(s): Ryosuke Sato, Akira Fukao, Akio Nomoto, Toshinobu Fujiwara
  • 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（福岡）
  • Year and Date: 2012-12-12
• [Presentation] The essential role for RNA triphosphatase Cet1p in nuclear import of capping enzyme complex in Saccharomyces cervisiae. (2012)
  • Author(s): Naoki Takizawa, Toshinobu Fujiwara, Manabu Yamasaki, Kiyohisa Mizumoto, Akio Nomoto
  • 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（福岡）
  • Year and Date: 2012-12-12
• [Presentation] Analyses of underlying relationship between the subcellular localization and stimulatory activity on cap-dependent translation of RNA-binding protein HuD (2012)
  • Author(s): Ryosuke Sato, Akira Fukao, Akio Nomoto, Toshinobu Fujiwara
  • Organizer: The EMBO/EMBL Symposium "Complex Life of mRNA"
  • Place of Presentation: EMBL Heidelberg (Germany)
  • Year and Date: 2012-10-07
• [Presentation] HuD accelerates cap-dependent translation through eIF4B phosphorylation by active Akt1. (2012)
  • Author(s): Akira Fukao, Toshinobu Fujiwara
  • Organizer: Cold Spring Harbor Laboratory Meetings Conferences: Translational Control
  • Place of Presentation: Cold Spring Harbor Laboratory NY (USA)
  • Year and Date: 2012-09-06
• [Presentation] Regulation of MAPK signaling by nuclear-cytoplasmic shuttling of the RNA-binding protein Rnc1 in fission yeast. (2012)
  • Author(s): Ryosuke Satoh, Yasuhiro Matsumura, Akitomo Tanaka, Nanae Umeda, Makoto Takada, Yuna Ito, Ayako Kita, Kanako Hagihara, Akira Doi, Toshinobu Fujiwara, Reiko Sugiura
  • Organizer: The 22nd CDB Meeting: RNA Sciences in Cell and Developmental Biology II
  • Place of Presentation: 理研CDB（神戸）
  • Year and Date: 2012-06-11
• [Book] 細胞工学「神経系の翻訳制御メカニズム」 (2012)
  • Author(s): 藤原俊伸
  • Total Pages: 9
  • Publisher: 学研メディカル秀潤社