mRNA surveillance system to ensure the fidelity of gene expression

• Project Area: Diversity and asymmetry achieved by RNA program
• Project/Area Number: 20112006
• 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: Tohoku University (2010-2012); Nagoya University (2008-2009)
• Principal Investigator: INADA Toshifumi 東北大学, 大学院・薬学研究科, 教授 (40242812)
• Project Period (FY): 2008 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥138,840,000 (Direct Cost: ¥106,800,000、Indirect Cost: ¥32,040,000); Fiscal Year 2012: ¥33,150,000 (Direct Cost: ¥25,500,000、Indirect Cost: ¥7,650,000); Fiscal Year 2011: ¥33,150,000 (Direct Cost: ¥25,500,000、Indirect Cost: ¥7,650,000); Fiscal Year 2010: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000); Fiscal Year 2009: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000); Fiscal Year 2008: ¥28,340,000 (Direct Cost: ¥21,800,000、Indirect Cost: ¥6,540,000)
• Keywords: mRNA品質管理 / 翻訳アレスト / 新生ポリペプチド鎖 / mRNA分子内切断 / ユビキチン化 / プロテアソーム / リボソーム / リボソーム解離因子 / 異常RNA分解 / 異常タンパク質分解 / ユビキチン化ビキチン化 / RNA / 翻訳伸長阻害 / RMA品質管理 / タンパク質分解 / mRNA分解 / E3ユビキチンライゲース / mRNA分解制御 / 翻訳 / 翻訳伸長阻 / 翻訳制御 / 品質管理 / mRNA暗転性制御

Research Abstract

Cells have mRNA surveillance systems to recognize aberrant translation elongation and termination, and eliminate aberrant mRNAs. We have identified the novel factors to recognize and eliminate aberrant translation. We have demonstrated that rapid proteasomal degradation of aberrant proteins derived from aberrant mRNAs plays an important role in preventing the expression of abnormal proteins as well as rapid mRNA decay.

Research Products

• [Journal Article] Global microRNA elevation by inducible Exportin 5 regulates cell cycle entry (2013)
  • Author(s): Iwasaki, Y. W.; Kiga, K.; Kayo, H.; Fukuda-Yuzawa, Y.; Weise, J.; Inada, T.; Tomita, M.; Ishihama, Y..; Fukao, T.
  • Journal Title: RNA Volume: 19 (4) Issue: 4 Pages: 490-7
  • DOI: 10.1261/rna.036608.112
  • Peer Reviewed
• [Journal Article] A ribosome-bound quality control complex triggers nascent peptides and signals translation stress (2012)
  • Author(s): Brandman, O., Ornstein, JS., Wong, D., Larson, A., Williams, C. C, Li, GW., Zhou, S., King, D., Shen, P S, Weibezahn, J., Dunn, J.q Rouskin, S., Inada, T., Frost, A., Weissman, JS
  • Journal Title: Cell Volume: 151 Issue: 5 Pages: 1042-1054
  • DOI: 10.1016/j.cell.2012.10.044
  • Peer Reviewed
• [Journal Article] Dom34:Hbs1 Plays a General Role in Quality-Control Systems by Dissociation of a Stalled Ribosome at the 3' End of Aberrant mRNA (2012)
  • Author(s): Tatsuhisa Tsuboi, et al
  • Journal Title: Molecular Cell Volume: 46 Issue: 4 Pages: 1-12
  • DOI: 10.1016/j.molcel.2012.03.013
  • Peer Reviewed
• [Journal Article] Roles of dom34 : hbs1 in nonstop protein clearance from translocators for normal organelle protein influx. (2012)
  • Author(s): Toshiaki Izawa, Tatsuhisa Tsuboi, Kazushige Kuroha, et al.
  • Journal Title: Cell Reports Volume: 2 Issue: 3 Pages: 447-453
  • DOI: 10.1016/j.celrep.2012.08.010
  • Peer Reviewed
• [Journal Article] RACK1 stimulates nascent polypeptide-dependent translation arrest (2010)
  • Author(s): Kuroha, K., Akamatsu, M., Dimitrova, L, lto, T.,Kato, Y Shirahige, K. and lnada. T
  • Journal Title: EMBO. Rep Volume: 11 Issue: 12 Pages: 956-961
  • DOI: 10.1038/embor.2010.169
  • Peer Reviewed
• [Journal Article] Dual functions of yeast tRNA ligase in the unfolded protein response: unconventional cytoplasmic splicing of HAC1 pre-mRNA is not sufficient to release translational attenuation (2010)
  • Author(s): Mori T, Ogasawara C, lnada, T, Englert M, Beier H, Takezawa M, Endo T, Yoshihisa T
  • Journal Title: Mol. Biol. Cell Volume: 21 Issue: 21 Pages: 3722-3734
  • DOI: 10.1091/mbc.e10-08-0693
  • Peer Reviewed
• [Journal Article] Stmctural Basis for mRNA Surveillance by Archaeal Pelota and GTP-bound EF1α Complex (2010)
  • Author(s): Kobayashi, K. Kikuno,1. Kuroha, K. Saito, K. Ito, K. Ishitani, R. Inada. T. and Nureki, O
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Issue: 41 Pages: 17575-17579
  • DOI: 10.1073/pnas.1009598107
  • Peer Reviewed
• [Journal Article] Tethering of poly(A) binding protein interferes with non-translated mRNA decay from 5' end in yeast (2010)
  • Author(s): Tsuboi, T. and Inada, T
  • Journal Title: J. Biol. Chem Volume: 285 Issue: 44 Pages: 33589-33601
  • DOI: 10.1074/jbc.m110.117150
  • Peer Reviewed
• [Journal Article] RACK1 stimulates nascent polypeptide-dependent translation arrest. (2010)
  • Author(s): Kuroha, K., Akamatsu, M., Dimitrova, L., Ito, T., Kato, Y.Shirahige, K., Inada, T.
  • Journal Title: EMBO Reports 11 Pages: 956-961
  • Peer Reviewed
• [Journal Article] Structural Basis for mRNA Surveillance by Archaeal Pelota and GTP-bound EF1α Complex. (2010)
  • Author(s): Kobayashi, K.Kikuno, I.Kuroha, K.Saito, K.Ito, K.Ishitani, R.Inada, T., Nureki, O.
  • Journal Title: Proc.Natl.Acad.Sci.USA 107 Pages: 17575-17579
  • Peer Reviewed
• [Journal Article] Tethering of poly(A) binding protein interferes with non-translated mRNA decay from 5' end in yeast. (2010)
  • Author(s): Tsuboi, T., Inada, T.
  • Journal Title: J.Biol.Chem. 285 Pages: 33589-33601
  • Peer Reviewed
• [Journal Article] RACK1 stimulates nascent polypeptide-dependent translation arrest (2010)
  • Author(s): Kuroha, K., Akamatsu, M., Dimitrova, L., Ito, T., Kato, Y.Shirahige, K., Inada, T.
  • Journal Title: EMBO Reports Volume: 11 Pages: 956-961
  • Peer Reviewed
• [Journal Article] Structural Basis for mRNA Surveillance by Archaeal Pelota and GTP-bound EF1α Complex (2010)
  • Author(s): Kobayashi, K.Kikuno, I.Kuroha, K.Saito, K.Ito, K.Ishitani, R.Inada, T., Nureki, O.
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 107 Pages: 17575-17579
  • Peer Reviewed
• [Journal Article] Tethering of poly (A) binding protein interferes with non-translated mRNA decay from 5' end in yeast (2010)
  • Author(s): Tsuboi, T., Inada, T
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 33589-33601
  • Peer Reviewed
• [Journal Article] Upflp stimulates proteasome-mediated degradation of the product derived from the specific nonsense-containing mRNA (2009)
  • Author(s): Kuroha, K., Tatematsu, T. and lnada, T
  • Journal Title: EMBO Rep Volume: 10 Issue: 11 Pages: 1265-1271
  • DOI: 10.1038/embor.2009.200
  • Peer Reviewed
• [Journal Article] Nascent peptide-dependent translation arrest leads to not4p-mediated protein degradation by the proteasome (2009)
  • Author(s): Dimitrova, L, Kuroha, K., Tatematsu, T. and lnada, T
  • Journal Title: J. Biol. Chem Volume: 284 Issue: 16 Pages: 10343-10352
  • DOI: 10.1074/jbc.m808840200
  • Peer Reviewed
• [Journal Article] Nucleolar structure and function regulated by a deubiquitinating enzyme USP36 (2009)
  • Author(s): Endo, A., Matsumoto, M, Inada. T., Yamamoto, A., Nakayama, K.I., Kitamura, N. and Komada, M
  • Journal Title: J. Cell. Sci Volume: 122 Issue: 5 Pages: 678-685
  • DOI: 10.1242/jcs.044461
  • Peer Reviewed
• [Journal Article] I Analysis of nonstop mRNA translation in the absence of tmRNA in E.coli (2009)
  • Author(s): Kuroha, K., Horiguchi, N., Aiba, H. and Inada, T
  • Journal Title: Genes Cells Volume: 14 Pages: 739-749
  • Peer Reviewed
• [Journal Article] Upf1p stimulates proteasome-mediated degradation of the product derived from the specific nonsense-containing mRNA. (2009)
  • Author(s): Kuroha, K., Tatematsu, T., Inada, T.
  • Journal Title: EMBO Reports 10 Pages: 1265-1271
  • Peer Reviewed
• [Journal Article] Nascent peptide-dependent translation arrest leads to not4p-mediated protein degradation by the proteasome. (2009)
  • Author(s): Dimitrova, N., Kuroha, K., Tatematsu, T., Inada, T.
  • Journal Title: J.Biol.Chem. 284 Pages: 10343-10352
  • Peer Reviewed
• [Journal Article] Analysis of nonstop mRNA translation in the absence of tmRNA in E.coli. (2009)
  • Author(s): Kuroha, K., Horiguchi, N., Aiba, H., Inada, T.
  • Journal Title: Genes to Cells 14 Pages: 739-749
  • Peer Reviewed
• [Journal Article] Upflp stimulates proteasome-mediated degradation of the product derived from the specific nonsense-containing mRNA. (2009)
  • Author(s): Kuroha, K., Tatematsu, T., Inada, T.
  • Journal Title: EMBO report 10 Pages: 1265-1271
  • Peer Reviewed
• [Journal Article] Analysis of nonstop mRNA translation in the absence of tmRNA in E.coli. (2009)
  • Author(s): Kuroha, K., Horiguchi, N., Aiba, H., *Inada, T.
  • Journal Title: Genes to Cells 14 Pages: 739-749
  • Peer Reviewed
• [Journal Article] Nascent peptide-dependent translation arrest leads to not 4 p-mediated protein degradation by the proteasome (2009)
  • Author(s): Dimitrova, L., Kuroha, K., Tatematsu, T. and Inada, T.
  • Journal Title: J. Biol. Chem. 284 Pages: 10343-10352
  • Peer Reviewed
• [Journal Article] Semaphorin controls epidermal morphogenesis by stimulating mRNA translation via eIF2a in Caenorhabditis elegans (2008)
  • Author(s): Nukazuka, A., Fujisawa, H., Inada, T., Oda, Y, Takagi, S
  • Journal Title: Genes Dev Volume: 22 Issue: 8 Pages: 1025-1036
  • DOI: 10.1101/gad.1644008
  • Peer Reviewed
• [Journal Article] Semaphorin controls epidermal morphogenesis by stimulating mRNA translation via eIF2a in C.elegans. (2008)
  • Author(s): Nukazuka, A.Fujisawa, H.Inada, T.Oda, Y.Takagi, S.
  • Journal Title: Genes Dev. 22 Pages: 1025-1036
  • Peer Reviewed
• [Presentation] Protein quality control systems coupled with No-Go and Non-Stop mRNA surveillance in yeast (2012)
  • Author(s): 稲田利文
  • Organizer: Quality control
  • Place of Presentation: Heidelberg, Germany
  • Year and Date: 2012-09-19
• [Presentation] Dom34:Hbs1 Plays a General Role in Quality Control Systems by Dissociation of a Stalled Ribosome at the 3’ End of Aberrant mRNA (2012)
  • Author(s): 稲田利文
  • Organizer: Protein synthesis and translational control
  • Place of Presentation: CSH, NY, USA
  • Year and Date: 2012-09-04
• [Presentation] Stalled ribosomes induce the degradation of aberrant mRNA and protein (2012)
  • Author(s): 稲田利文
  • Organizer: FASB meeting mechanism of mRNA decay
  • Place of Presentation: Colorado, USA
  • Year and Date: 2012-06-24
• [Presentation] Stalled ribosomes induce mRNA and protein quality control systems (2012)
  • Author(s): 稲田利文
  • Organizer: Jacques Monod conferences 25th anniversary
  • Place of Presentation: Roscoff, France
  • Year and Date: 2012-06-02
• [Presentation] 終止コドン非依存サブユニット解離による異常mRNA分解促進機構 (2012)
  • Author(s): 坪井達久、池内健、黒羽一誠、鹿島勲、工藤和兵、牧野志保、井上絵里、稲田利文
  • Organizer: Ribosome meeting
  • Place of Presentation: 広島、日本
  • Year and Date: 2012-03-16
• [Presentation] Novel roles of Dom34:Hbs1 and RACK1 in mRNA quality control systems (2012)
  • Author(s): 稲田利文
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド、神戸
• [Presentation] Protein quality control systems coupled with No-Go and Non-Stop mRNA surveillance in yeast (2012)
  • Author(s): Inada. T
  • Organizer: EMBO meeting on 'Quality control'
  • Place of Presentation: EMBL, Heidelberg, Germany
• [Presentation] Dom34:Hbs1 Plays a General Role in Quality Control Systems by Dissociation of a Stalled Ribosome at the 3'End of Aberrant mRNA (2012)
  • Author(s): Inada, T
  • Organizer: Protein synthesis and translational control
  • Place of Presentation: Cold Spring Harbor, NewYork, USA
• [Presentation] Quality control of mRNA and protein in eukaryotes (2012)
  • Author(s): Inada, T
  • Organizer: The 22nd CDB meeting on"RNA Sciences in Cell and Developmental Biology II
  • Place of Presentation: Kobe, Japan
• [Presentation] Stalled ribosomes induce mRNA and protein quality control systems (2012)
  • Author(s): Inada, T
  • Organizer: Jacques Monod conferences 25th anniversary
  • Place of Presentation: Roscoff, France
• [Presentation] The mechanism of quality control coupled with translation arrest in yeast (2011)
  • Author(s): Toshifumi Inada
  • Organizer: ISNAC2011
  • Place of Presentation: 札幌、日本(招待講演)
  • Year and Date: 2011-11-10
• [Presentation] RNAの識別と管理-自己、異常な自己、そして非自己- (2011)
  • Author(s): 稲田利文
  • Organizer: フォーラムinドージン
  • Place of Presentation: 熊本、日本(招待講演)
  • Year and Date: 2011-11-04
• [Presentation] Dual function of Dom34:Hbs1 complex in mRNA clearance coupled with translation arrest in yeast (2011)
  • Author(s): Toshifumi Inada
  • Organizer: Protein Synthesis and Translational Control Meeting
  • Place of Presentation: EMBL, Heidelberg, Germany
  • Year and Date: 2011-09-08
• [Presentation] The novel roles of Dom34:Hbs1 complex in No-Go-Decay quality control systems in yeast (2011)
  • Author(s): Tatsuhisa Tsuboi, Isao Kashima, Kazushige Kuroha, Shiho Makino, Kazuhei Kudo, Toshifumi Inada
  • Organizer: mRNA processing Meeting
  • Place of Presentation: CSHL, NY, USA
  • Year and Date: 2011-08-24
• [Presentation] Dual functions of Dom34:Hbs1 complex in mRNA clearance coupled with translation arrest in yeast (2011)
  • Author(s): Toshifumi Inada
  • Organizer: RNA Society Meeting 2011
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2011-06-17
• [Presentation] 1W20 異常翻訳の認識と品質管理機構におけるDom34/Hbs1複合体の新たな役割 (2010)
  • Author(s): 稲田利文
  • Organizer: BMB2010(日本分子生物学会・日本生化学会、合同年会)
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-12-07
• [Presentation] 1W20 翻訳の分子基盤からRNA品質管理機構の理解へ (2010)
  • Author(s): 稲田利文
  • Organizer: BMB2010(日本分子生物学会・日本生化学会、合同年会)
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-12-07
• [Presentation] 40S-ribosome-bound RACK1 functions in nascent peptide-dependent translation arrest that leads to Dom34/Hbs1-independent NGD (2010)
  • Author(s): 稲田利文
  • Organizer: Translational Control Meeting
  • Place of Presentation: CSHL, NY, USA
  • Year and Date: 2010-09-15
• [Presentation] Rack1 participates in nascent polypeptide-dependent translation arrest (2010)
  • Author(s): 稲田利文
  • Organizer: Ribosome 2010
  • Place of Presentation: Orvieto, Italy
  • Year and Date: 2010-05-15
• [Presentation] 12S12p 多様性と非対称性を獲得するRNAプログラム「新生ポリペプチド鎖依存翻訳アレスト因子RACK1の同定」 (2009)
  • Author(s): 稲田利文
  • Organizer: 第82回日本生化学会シンポジウム
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2009-10-22
• [Presentation] 40S ribosome-bound RACK1 functions in nascent peptide-dependent translation arrest (2009)
  • Author(s): 稲田利文
  • Organizer: Translational control meeting
  • Place of Presentation: EMBL, Hidelberg, Germany
  • Year and Date: 2009-09-05
• [Presentation] 40S ribosome-bound RACK1 functions in nascent peptide-dependent translation arrest that leads to Hbs1/Dom34-independent NGD (2009)
  • Author(s): 稲田利文
  • Organizer: Eukaryotic mRNA processing
  • Place of Presentation: CSHL, NY, USA
  • Year and Date: 2009-08-20
• [Presentation] Nascent peptide-dependent translation arrest leads to Not 4 p-mediated protein degradation by the proteasome (2008)
  • Author(s): Kazushige Kuroha, Lyudmil Dimitrova, Tsuyako Tatematsu, Toshifumi Inada
  • Organizer: BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Book] 「RNA品質管理機構iにおける停滞リボソーム解離複合体の普遍的機能」 生化学 (2012)
  • Author(s): 稲田利文
  • Publisher: 日本生化学学会
• [Book] 「RNA品質管理機構とあらたな遺伝子疾患治療薬の開発」医学のあゆみ『RNA医学・医療一あらたな診断治療を拓く』 (2011)
  • Author(s): 稲田利文
  • Publisher: 医歯薬出版株式会社
• [Book] 蛋白質核酸酵素増刊号『mRNAプログラムー多様性と非対称性の獲得戦略一』 (2009)
  • Author(s): 稲田利文、大野睦人編
  • Publisher: 共立出版
• [Book] 多様性と非対称性を獲得するRNAプログラム(概論:遺伝子発現制御の中核をなすRNAプログラム)(蛋白質核酸酵素増刊号) (2009)
  • Author(s): 稲田利文
  • Publisher: 共立出版社
• [Book] 多様性と非対称性を獲得するRNAプログラム(RNAプログラムを支える品質管理機構)(蛋白質核酸酵素増刊号) (2009)
  • Author(s): 稲田利文
  • Publisher: 共立出版社
• [Book] 蛋白質核酸酵素増刊号『多様性と非対称性を獲得するRNAプログラム』 (2009)
  • Author(s): 稲田利文
  • Publisher: 共立出版
• [Book] 「転写後制御を標的とした遺伝子疾患治療一異常mRNAから正常なタンパク質を合成させる低分子化合物」実験医学増刊『RNAの機能解明と医療応用』 (2008)
  • Author(s): 稲田利文
  • Publisher: 羊土社
• [Book] 「mRNAの動態とプロテアソーム」実験医学増刊『タンパク質の分解機構』 (2008)
  • Author(s): 稲田利文
  • Publisher: 羊土社
• [Book] RNAの機能解明と医療応用(転写後制御を標的とした遺伝子疾患治療─異常mRNAから正常なタンパク質を合成させる低分子化合物)(実験医学増刊) (2008)
  • Author(s): 稲田利文
  • Publisher: 羊土社
• [Book] タンパク質の分解機構(実験医学増刊)(mRNAの動態とプロテアソーム) (2008)
  • Author(s): 稲田利文
  • Publisher: 羊土社
• [Remarks]
• [Remarks] 遺伝子制御薬学分野HP
  • URL: http://www.pharm.tohoku.ac.jp/~idenshi/inada_lab_HP/HOME(Japanese).html
• [Remarks]
  • URL: http://www.pharm.tohoku.ac.jp/~idenshi/idenshi-j.shtml
• [Remarks]
  • URL: http://web.me.com/toshiinada/Inada_Lab/Home.html
• [Remarks]
  • URL: http://www.org.kobe-u.ac.jp/rna/