mRNA surveillance system to ensure the fidelity of gene expression

2012 Fiscal Year Final Research Report

• 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
• 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

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] 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 Pages: 1042-1054
  • DOI: 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 Stalled Ribosome at 3'End of Aberrant mRNA (2012)
  • Author(s): Tsuboi, T., Kuroha, K., Kudo, K., Makino S., Inoue, E, Kashima, I. and Inada, T
  • Journal Title: Mol. Cell Volume: 26 Pages: 518-529
  • DOI: 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): Izawa, T. Tsuboi, T. Kuroha, K. lnada, T. Nishikawa, SI. Endo, T
  • Journal Title: Cell Rep Volume: 2 Pages: 447-453
  • DOI: 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 Pages: 956-961
  • DOI: 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 Pages: 3722-3734
  • DOI: 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 Pages: 17575-17579
  • DOI: 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 Pages: 33589-33601
  • DOI: doi:10.1074/jbc.M110.117150
  • 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 Pages: 1265-1271
  • DOI: 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 Pages: 10343-10352
  • DOI: 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 Pages: 678-685
  • DOI: 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
  • DOI: doi:10.1111/j.1365-2443.2009.01304
  • 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 Pages: 1025-1036
  • DOI: doi:10.1101/gad.1644008
  • Peer Reviewed
• [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
  • Year and Date: 20121211-14
• [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
  • Year and Date: 20120919-22
• [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
  • Year and Date: 20120904-08
• [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
  • Year and Date: 20120611-13
• [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
  • Year and Date: 20120602-06
• [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
  • Total Pages: 84:790-793
  • 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
  • Total Pages: 238:413-417
  • 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
  • Total Pages: 54,2013-2252
  • 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
  • Total Pages: 26:1644-1649
  • 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
  • Total Pages: 26:237-241
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.pharm.tohoku.ac.jp/～idenshi/inada_lab_HP/HOME(Japanese).html