New roles of RNAs in metabolic regulation

• Project/Area Number: 17207010
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Nagoya University
• Principal Investigator: AIBA Hiroji Nagoya University, 大学院・理学研究科, 教授 (20025662)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥50,700,000 (Direct Cost: ¥39,000,000、Indirect Cost: ¥11,700,000); Fiscal Year 2008: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000); Fiscal Year 2007: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000); Fiscal Year 2006: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000); Fiscal Year 2005: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
• Keywords: small RNA / 翻訳制御 / mRNA分解 / Hfq / 塩基対形成 / グルコース応答 / 代謝ストレス / tmRNA / 品質管理 / RNase E / グルコーストランスポーター / 解糖系 / 翻訳抑制 / ribonucleoprotein complex

Research Abstract

大腸菌tmRNA とリボソームによる翻訳とmRNA 分解制御について解析し、翻訳途上のリボソームが停滞した際にmRNA の切断を誘起し、tmRNA 系と連動してmRNA とタンパク質の双方を分解するというより巧妙な品質管理機構として働いていることを明らかにした。具体的には、翻訳終結因子RF の活性低下、連続するレアコドンを持つmRNA の翻訳、あるいはアミノ酸枯渇により生じるリボソームの停滞に応答していずれの場合にもmRNA が切断されることを見いだし、翻訳伸長の遅延あるいは停滞によるmRNA の切断と分解が普遍的な機構であることを示した。また、グルコース-6-リン酸の異常な蓄積により合成が誘導され、ptsG mRNA を標的としているHfq 結合性小分子RNA(sRNA)であるSgrS による翻訳抑制とmRNA の分解について解析し、SgrS が、ptsG mRNA の翻訳開始領域と部分的な塩基対を形成し、Rnase E に依存したmRNA の不安定化をもたらすこと、SgrS がHfq を介してRnase E と相互作用すること、SgrSによるptsG mRNA の抑制機構において、ptsG mRNA の翻訳阻害が第一義的であること、HfqがSgrS とptsG mRNA の塩基対形成を促進すること、さらには、ptsG mRNA の膜局在性がSgrSのptsG mRNA への効果的な作用に寄与していることなどを明らかにした。

Research Products

• [Journal Article] Analyses of mRNA destabilization and translational inhibition mediated by Hfq-binding small RNAs (2008)
  • Author(s): Morita, T., Maki, K., Yagi, M. and Aiba, H.
  • Journal Title: Methods Enzymol 447 Pages: 359-378
• [Journal Article] RNA but not protein partners are directly responsible for translational silencing by a bacterial Hfq-binding small RNA (2008)
  • Author(s): Maki, K., Uno, K., Morita, T., and Aiba, H
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 10332-10337
• [Journal Article] Cleavage of mRNAs and role of tmRNA system under amino acid starvation in Escherichia coli (2008)
  • Author(s): Li, X., Yagi, M, T., Morita, T., and Aiba, H
  • Journal Title: Mol. Microbiol 68 Pages: 462-473
• [Journal Article] Cleavage of mRNAs and role of tmRNA system under aminoacid starvation in Escherichia coli (2008)
  • Author(s): Li, X., Yagi, M, T., Morita, T., Aiba. H.
  • Journal Title: Mol. Microbiol. 68 Pages: 462-473
  • Peer Reviewed
• [Journal Article] RNA but not protein partners are directly responsible for transla tional silencing by a bacterial Hfq-binding small RNA. (2008)
  • Author(s): Maki, K., Uno, K., Morita, T., Aiba, H.
  • Journal Title: Proc. Natl. Acad. Sri. USA 105 Pages: 10332-10337
  • Peer Reviewed
• [Journal Article] Analyses of mRNA destabilization and translational inhibition mediated by Hfq-binding small RNAs. (2008)
  • Author(s): Morita, T., Maki, K., Yagi, M. Aiba. H.
  • Journal Title: Methods Enzymol. 447 Pages: 359-378
  • Peer Reviewed
• [Journal Article] Cleavage of mRNAs and role of tmRNA system under amino acid starvation in Escherichia coli. (2008)
  • Author(s): Li, X., Yagi, M, T., Morita, T., and Aiba, H.
  • Journal Title: Mol. Microbiol 68 Pages: 462-473
  • Peer Reviewed
• [Journal Article] Small RNAs making a small protein (2007)
  • Author(s): Morita, T., and Aiba, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 20149-20150
• [Journal Article] Mechanism of RNA silencing by Hfq-binding small RNAs (2007)
  • Author(s): Aiba, H
  • Journal Title: Curr. Opin. Microbiol 10 Pages: 134-139
• [Journal Article] Reduced action of polypeptide release factors induces mRNA cleavage and tmRNA tagging at stop codons in Escherichia coli (2007)
  • Author(s): Li, X., Yokota, T., Ito, K., Nakamura, Y., and Aiba, H
  • Journal Title: Mol. Microbiol 63 Pages: 116-126
• [Journal Article] 大腸菌低分子RNAによる遺伝子発現抑制機構 (2007)
  • Author(s): 森田鉄兵, 饗場弘二
  • Journal Title: 化学と生物 45 Pages: 298-300
• [Journal Article] Reduced action of polypeptide release factors induces mRNA cleavage and tmRNA tagging at stop codons in Escherichia coli. (2007)
  • Author(s): Li, X., Teruaki Yokota, T., Ito K., Nakamura Y., and Aiba, H.
  • Journal Title: Mol. Microbiol 63 Pages: 116-126
  • Peer Reviewed
• [Journal Article] Mechanism of RNA silencing by Hfq-binding small RNAs. (2007)
  • Author(s): Aiba, H.
  • Journal Title: Curr. Opin. Microbiol 10 Pages: 134-139
  • Peer Reviewed
• [Journal Article] Small RNAs making a small protein. (2007)
  • Author(s): T., Morita, T., and Aiba, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 20149-20150
  • Peer Reviewed
• [Journal Article] Reduced action of polypeptide release factors induces mRNA cleavage and tmRNA tagging at stop codons in Escherichia coli. (2007)
  • Author(s): Li, X., Teruaki Yokota T., Ito K., Nakamura Y., Aiba, H.
  • Journal Title: Mol. Microbiol. 63 Pages: 116-126
• [Journal Article] 大腸菌smallRNAによるRNA サイレンシングの分子機構 (2006)
  • Author(s): 森田鉄兵、饗場弘二
  • Journal Title: 蛋白質 核酸 酵素 51 Pages: 2478-2483
  • NAID: 10019309982
• [Journal Article] Protein tagging at rare codons is caused by tmRNA action at the 3' end of nonstop mRNA generated in response to ribosome stalling. (2006)
  • Author(s): Li, X., Hirano, R., Tagami, H., Aiba, H.
  • Journal Title: RNA 12 Pages: 248-255
• [Journal Article] Translational repression is sufficient for gene silencing by bacterial small non-coding RNAs in the absence of mRNA destruction. (2006)
  • Author(s): Morita, T., Mochizuki, Y., Aiba, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 103 Pages: 4858-4863
• [Journal Article] Yeel, a novel protein involved in modulation of the activity of the glucose-phosphotransferase system in Escherichia coli K-12. (2006)
  • Author(s): Becker.A.K., Zeppenfeld, T., Staab, A., Seitz, S., Boos, W., Morita T., Aiba H., Mahr, K., Titgemeyer, F., Jahreis, K.
  • Journal Title: J Bacteriol. 188 Pages: 5439-5449
• [Journal Article] Base-pairing requirement for RNA silencing by a bacterial small RNA and acceleration of duplex formation by Hfq. (2006)
  • Author(s): Kawamoto, H., Koide, Y., Morita, T., Aiba, H.
  • Journal Title: Mol. Microbiol. 61 Pages: 1013-1022
• [Journal Article] Protein tagging at rare codons is caused by tmRNA action at the 3' end of nonstop mRNA generated in response to ribosome stalling. (2006)
  • Author(s): Li, X., Hirano, R., Tagami, H, Aiba, H.
  • Journal Title: RNA 12 Pages: 248-255
• [Journal Article] Translational repression is sufficient for gene silencing by bacterial small non-coding RNAs in the absence of mRNA destruction. (2006)
  • Author(s): Morita, T., Mochizuki, Y., Aiba, H.
  • Journal Title: Proc.Natl.Acad.Sci.USA. (in press)
• [Journal Article] グルコース応答と代謝制御ネットワークの新しい世界 (2005)
  • Author(s): 森田鉄兵、饗場弘二
  • Journal Title: 化学と生物 43 Pages: 222-228
  • NAID: 10019045282
• [Journal Article] Implication of membrane localization of target mRNA in the action of a small RNA : mechanism of post-transcriptional regulation of glucose transporter in Escherichia coli. (2005)
  • Author(s): Kawamoto, H., Morita, T., Shimizu, A., Inada, T., Aiba, H.
  • Journal Title: Genes Dev. 19 Pages: 328-338
• [Journal Article] Translation of aberrant mRNAs lacking a termination codon or with a shortened 3'-UTR is repressed after initiation in yeast. (2005)
  • Author(s): Inada, T., Aiba, H.
  • Journal Title: EMBO J. 24 Pages: 1584-1595
• [Journal Article] RNase E-based ribonucleoprotein complexes : mechanical basis of mRNA destabilization mediated by bacterial noncoding RNAs. (2005)
  • Author(s): Morita, T., Maki, K., Aiba, H.
  • Journal Title: Genes Dev. 19 Pages: 2176-2186
• [Journal Article] (2006) Base-pairing requirement for RNA silencing by a bacterial small RNA and acceleration of duplex formation by Hfq
  • Author(s): Kawamoto, H., Koide, Y., Morita, T., and Aiba, H.
  • Journal Title: Mol. Microbiol 61 Pages: 1013-1022
• [Journal Article] (2006) YeeI, a novel protein involved in modulation of the activity of the glucose-phosphotransferase system in Escherichia coli K-12
  • Author(s): Becker. A. K., Zeppenfeld, T., Staab, A., Seitz, S., Boos, W., Morita T., Aiba, H Mahr, K., Titgemeyer, F., and Jahreis, K
  • Journal Title: J Bacteriol 188 Pages: 5439-49
• [Journal Article] (2006) Translational repression is sufficient for gene silencing by bacterial small non-coding RNAs in the absence of mRNA destruction
  • Author(s): Morita, T., Mochizuki, Y., and Aiba, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 4858-4863
• [Journal Article] (2006) Protein tagging at rare codons is caused by tmRNA action at the 3' end of nonstop
  • Author(s): Li, X., Hirano, R., Tagami, H., and Aiba, H
  • Journal Title: mRNA generated in response to ribosome stalling. RNA 12 Pages: 248-255
• [Journal Article] (2005) Rnase E-based ribonucleoprotein complexes : mechanicalbasis of mRNA destabilization mediated by bacterial noncoding RNAs
  • Author(s): Morita, T., Maki, K., and Aiba, H
  • Journal Title: Genes Dev 19 Pages: 2176-86
• [Journal Article] (2005) Translation of aberrant mRNAs lacking a termination codon or with a shortened 3'-UTR is repressed after initiation in yeast
  • Author(s): Inada, T and Aiba, H.
  • Journal Title: EMBO J 24 Pages: 1584-95
• [Journal Article] (2005) Implication of membrane localization of target mRNA in the action of a small RNA : mechanism of post-transcriptional regulation of glucose transporter in Escherichia coli
  • Author(s): Kawamoto, H., Morita, T., Shimizu, A., Inada, T. and Aiba, H
  • Journal Title: Genes Dev 19 Pages: 328-338
• [Presentation] Mechanism and role of mRNA degradation mediated by Hfq-binding small RNAs in E. coli. JSPS-DST Asian Academic Seminar (2008)
  • Author(s): Aiba, H
  • Organizer: Genome Regulation :From Nanobiology to Pathogenesis
  • Place of Presentation: Bangalore, India
• [Presentation] Mechanism and role of mRNA degradation mediated by Hfq-binding small RNAs in E. coli (2008)
  • Author(s): Aiba, H
  • Organizer: FASEB Summer Research Conferences : Post-Transcriptional Control of Gene Expression : Mechanisms of mRNA Decay
  • Place of Presentation: Lucca, Italy
• [Presentation] Mechanism and role of mRNA degradation mediated by Hfq-bindlngsmall RNAs in E. coli. : Post-Transcriptional Control of Gene Expression : Mechanisms of mRNA Decay・ (2008)
  • Author(s): Aiba. H.
  • Organizer: FASEB Summer Research Conferences
  • Place of Presentation: Lucca, Italy
• [Presentation] Mechanism and role of mRNA degradation mediated by Hfq-binding small RNAs in E. coli. (2008)
  • Author(s): Aiba, H.
  • Organizer: JSPS-DST Asian Academic Seminar
  • Place of Presentation: Bangalore, India
• [Presentation] Mechanism of gene silencing mediated by Hfq-binding small RNAs in Escherichia coli (2007)
  • Author(s): Aiba, H
  • Organizer: Lecture in Cinvestav
  • Place of Presentation: Mexico
  • Year and Date: 2007-11-22
• [Presentation] Mechanism of RNA silencing mediated by Hfq-binding small RNAs in Escherichia coli (2007)
  • Author(s): Aiba, H
  • Organizer: 2007 Mini-Sympojium "Stimuli-Responsive Regulation of Gene Expression in Bacteria"
  • Place of Presentation: Soul National University, Korea
  • Year and Date: 2007-05-09
• [Presentation] Mechanism of RNA silencing mediated by Hfq-binding small RNAs in Escherichia coli (2007)
  • Author(s): Aiba, H
  • Organizer: 2007 International Meeting of the Microbiological Society of Korea
  • Place of Presentation: PyoeongChang, Korea
• [Presentation] Mechanism of RNA silencing mediated by Hfq-binding small RNAs in Escherichia coli (2007)
  • Author(s): Aiba, H
  • Organizer: VAAM2007
  • Place of Presentation: Osnabruek, Germany
• [Presentation] 大腸菌small RNAによる遺伝子発現抑制の分子機構 (2007)
  • Author(s): 饗場弘二
  • Organizer: RNA学会年会
  • Place of Presentation: 名古屋国際会議場、愛知
• [Presentation] Small RNAによる遺伝子サイレンシングの再構成:SgrSによるptsG mRNAの翻訳阻害は塩基対形成のみで起こる (2007)
  • Author(s): 牧貴美香、森田鉄兵、宇野可奈子、饗場弘二
  • Organizer: RNA学会年会
  • Place of Presentation: 名古屋国際会議場、愛知
• [Presentation] Upflpはプロテアソームによる翻訳に共役したナンセンス変異依存タンパク質分解を促進する (2007)
  • Author(s): 黒羽一誠、立松律弥子、水本英典、饗場弘二、稲田利文
  • Organizer: RNA学会年会
  • Place of Presentation: 名古屋国際会議場、愛知
• [Presentation] 塩基性アミノ酸の連続配列は翻訳アレストとタンパク質分解を起こす (2007)
  • Author(s): Lyudmila Dimitrova、黒羽一誠、立松律弥子、饗場弘二、稲田利文
  • Organizer: RNA学会年会
  • Place of Presentation: 名古屋国際会議場、愛知
• [Presentation] PTCをもっ異常mRNAと翻訳産物のUpf1依存の分解は、異常ORFの5'末端への正常なORFの挿入により抑制される (2007)
  • Author(s): 水本英典、立松律弥子、黒羽一誠、饗場弘二、稲田利文
  • Organizer: RNA学会年会
  • Place of Presentation: 名古屋国際会議場、愛知
• [Presentation] RNAサイレンシングに対する塩基対形成領域の位置効果 (2007)
  • Author(s): 高木智弘、森田鉄兵、饗場弘二
  • Organizer: RNA学会年会
  • Place of Presentation: 名古屋国際会議場、愛知
• [Presentation] RNase EのHfq結合領域の同定 (2007)
  • Author(s): 八木美江子、森田鉄兵、饗場弘二
  • Organizer: RNA学会年会
  • Place of Presentation: 名古屋国際会議場、愛知
• [Presentation] Mechanisms of RNA silencing mediated by a stresss-induced Hfq-binding small RNA, SgrS, in E.coli (2006)
  • Author(s): Aiba, H
  • Organizer: EMBO Conference
  • Place of Presentation: Heidelberg, Germany
• [Presentation] Regulation of translation and mRNA stability by ribonucleoprotein complexes consisting of small RNA, Hfq, and Rnase E (2006)
  • Author(s): Aiba, H
  • Organizer: Workshop "Regulation of Gene Expression in Bacterial and Biodegradation of Contaminants in the Environment"
  • Place of Presentation: Baeza, Spain
• [Presentation] Regulation of translation and mRNA stability by bacterial sRNP consisting of a small non-coding RNA (2006)
  • Author(s): Aiba, H
  • Organizer: Hfq, and Rnase E. CNRS Conference Jacques Monod
  • Place of Presentation: Roscoff, France
• [Presentation] Regulation of translation and mRNA stability by bacterial RISC consisting of non-coding RNA (2005)
  • Author(s): Aiba, H
  • Organizer: Hfq, and Rnase E. IBPC seminar
  • Place of Presentation: Paris, France
  • Year and Date: 2005-11-10
• [Presentation] Regulation of translation and mRNA stability by bacterial RISC consisting of non-coding RNA (2005)
  • Author(s): Aiba, H
  • Organizer: Hfq, and Rnase E. ICM seminar, Uppsala University
  • Place of Presentation: Uppsala, Sweden
  • Year and Date: 2005-11-05
• [Presentation] Regulation of translation and mRNA stability by bacterial non-coding RNAs under stress conditions. Spaciotemporal Network of RNA (2005)
  • Author(s): Aiba, H
  • Organizer: Information Flow International Symposium 2005
  • Place of Presentation: Hirosaki
  • Year and Date: 2005-08-08
• [Presentation] Regulation of translation and mRNA stability by bacterial RISC consisting of non-coding RNA (2005)
  • Author(s): Aiba, H
  • Organizer: Hfq, and Rnase E 9^<th> ACT
  • Place of Presentation: Zhunan, Taiwan
• [Presentation] Glucose Metabolism and Hfq/Small RNA-Mediated Post-Transcriptional Gene Regulation (2005)
  • Author(s): Aiba, H
  • Organizer: 105^<th> ASM : Regulating RNA stability
  • Place of Presentation: Atlanta, USA
• [Presentation] Regulation of translation and mRNA stability by bacterial sRNP consisting of a small non-coding RNA
  • Author(s): Aiba, H
  • Organizer: Hfq, and Rnase E. CNRS-IBMC seminar
  • Place of Presentation: Strasbourg, France