Mechanism of Protein Function Expression by Regulation of Translation Dynamics

• Project/Area Number: 18H03984
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Taguchi Hideki 東京工業大学, 科学技術創成研究院, 教授 (40272710)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥44,330,000 (Direct Cost: ¥34,100,000、Indirect Cost: ¥10,230,000); Fiscal Year 2020: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000); Fiscal Year 2019: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000); Fiscal Year 2018: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
• Keywords: 翻訳 / リボソーム / 新生鎖 / 熱ショックタンパク質 / プロテオーム / セントラルドグマ / シャペロン / タンパク質フォールディング / 無細胞翻訳系 / プロテオミクス / RAN翻訳 / 非典型的翻訳 / 翻訳バイパス

Outline of Final Research Achievements

In recent years, a number of noncanonical translation dynamics have been unveiled, indicating that there is an unexplored field around translation. For example, we discovered that ribosomes are destabilized (Intrinsic ribosome destabilization: IRD) during translation of amino acid sequences rich in negatively charged amino acids, resulting in premature translation termination. In this study, we performed a comprehensive analysis of the regulation of translation dynamics, focusing on IRD and translation-coupled protein folding, including biochemistry, molecular biology, and proteome analysis, and obtained many important results.

Academic Significance and Societal Importance of the Research Achievements

タンパク質はリボソームで翻訳され、合成されたポリペプチド鎖がフォールディングして機能を発現するというのが基本である。しかし近年、翻訳の周辺には未開拓の生物学が拡がっており、細胞内のタンパク質の世界に関して新たな視点が加わり始めている。特に、非典型的な翻訳や翻訳に共役したタンパク質フォールディングは十分理解されておらず、研究の方法論も確立していないことが多い。本研究では、私たちが見つけた現象や手法を追究するだけでなく、これまで待望されていた方法論の開発にも注力した。得られた成果は基礎研究として重要なだけでなく、有用タンパク質の生産、創薬や疾患の治療戦略などにもつながる。

Research Products

• [Journal Article] Nascent polypeptide within the exit tunnel stabilizes the ribosome to counteract risky translation (2021)
  • Author(s): Chadani Yuhei、Sugata Nobuyuki、Niwa Tatsuya、Ito Yosuke、Iwasaki Shintaro、Taguchi Hideki
  • Journal Title: The EMBO Journal Volume: 40 Issue: 23 Pages: 1-13
  • DOI: 10.15252/embj.2021108299
  • Peer Reviewed
• [Journal Article] C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers (2021)
  • Author(s): Nanaura Hitoki、Aiba Yuichiro、Nakanishi Mari、Shiota Tomo、Hibino Masaki、Kikuchi Sotaro、Nagata Riko、Morikawa Naritaka、Iguchi Naohiko、Kiriyama Takao、Nagamori Shushi、Sugie Kazuma、Saio Tomohide、Yoshizawa Takuya、Mori Eiichiro et al.
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 5301-5301
  • DOI: 10.1038/s41467-021-25560-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acetate overflow metabolism regulates a major metabolic shift after glucose depletion in <i>Escherichia</i> ? <i>coli</i> (2021)
  • Author(s): Shimada Tomohiro、Nakazawa Kohta、Tachikawa Tomoyuki、Saito Natsumi、Niwa Tatsuya、Taguchi Hideki、Tanaka Kan
  • Journal Title: FEBS Letters Volume: 595 Issue: 15 Pages: 2047-2056
  • DOI: 10.1002/1873-3468.14151
  • Peer Reviewed
• [Journal Article] Proximity Histidine Labeling by Umpolung Strategy Using Singlet Oxygen (2021)
  • Author(s): Nakane Keita、Sato Shinichi、Niwa Tatsuya、Tsushima Michihiko、Tomoshige Shusuke、Taguchi Hideki、Ishikawa Minoru、Nakamura Hiroyuki
  • Journal Title: Journal of the American Chemical Society Volume: 143 Issue: 20 Pages: 7726-7731
  • DOI: 10.1021/jacs.1c01626
  • Peer Reviewed
• [Journal Article] Novel self-regulation strategy of a small heat shock protein for prodigious and rapid expression on demand (2021)
  • Author(s): Miwa Tsukumi、Taguchi Hideki
  • Journal Title: Current Genetics Volume: 67 Issue: 5 Pages: 723-727
  • DOI: 10.1007/s00294-021-01185-0
  • Peer Reviewed
• [Journal Article] Thioredoxin pathway in Anabaena sp. PCC 7120: activity of NADPH-thioredoxin reductase C (2021)
  • Author(s): Deschoenmaeker Frederic、Mihara Shoko、Niwa Tatsuya、Taguchi Hideki、Wakabayashi Ken-Ichi、Toyoshima Masakazu、Shimizu Hiroshi、Hisabori Toru
  • Journal Title: The Journal of Biochemistry Volume: － Issue: 6 Pages: 709-719
  • DOI: 10.1093/jb/mvab014
  • NAID: 40022687787
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The evolutionary conserved iron-sulfur protein TCR controls P700 oxidation in photosystem I (2021)
  • Author(s): Luu Trinh Mai Duy、Miyazaki Daichi、Ono Sumire、Nomata Jiro、Kono Masaru、Mino Hiroyuki、Niwa Tatsuya、Okegawa Yuki、Motohashi Ken、Taguchi Hideki、Hisabori Toru、Masuda Shinji
  • Journal Title: iScience Volume: 24 Issue: 2 Pages: 102059-102059
  • DOI: 10.1016/j.isci.2021.102059
  • Peer Reviewed / Open Access
• [Journal Article] Escherichia coli small heat shock protein IbpA is an aggregation‐sensor that self‐regulates its own expression at posttranscriptional levels (2020)
  • Author(s): Miwa Tsukumi、Chadani Yuhei、Taguchi Hideki
  • Journal Title: Molecular Microbiology Volume: 115 Issue: 1 Pages: 142-156
  • DOI: 10.1111/mmi.14606
  • Peer Reviewed
• [Journal Article] G-quadruple-proximity protein labeling based on peroxidase activity. (2020)
  • Author(s): Masuzawa, T., Sato, S., Niwa, T., Tagushi, H., Nakamura, H., Oyoshi, T.
  • Journal Title: Chem. Comm. Volume: 56 Issue: 78 Pages: 11641-11644
  • DOI: 10.1039/d0cc02571b
  • Peer Reviewed
• [Journal Article] Nascent SecM chain interacts with outer ribosomal surface to stabilize translation arrest (2020)
  • Author(s): Mikihisa Muta, Ryo Iizuka, Tatsuya Niwa, Yuanfang Guo, Hideki Taguchi, Takashi Funatsu
  • Journal Title: Biochemical Journal Volume: 477 Issue: 2 Pages: 557-566
  • DOI: 10.1042/bcj20190723
  • Peer Reviewed / Open Access
• [Journal Article] Dynamics of oligomer and amyloid fibril formation by yeast prion Sup35 observed by high-speed atomic force microscopy (2020)
  • Author(s): Konno H, Watanabe-Nakayama T, Uchihashi T, Okuda M, Zhu L, Kodera N, Kikuchi Y, Ando T, Taguchi H
  • Journal Title: Proc. Natl. Acad. Sci. U S A Volume: 117 Issue: 14 Pages: 7831-7836
  • DOI: 10.1073/pnas.1916452117
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Disruption of the gene trx-m1 impedes the growth of Anabaena sp. PCC 7120 under nitrogen starvation (2019)
  • Author(s): Deschoenmaeker Frederic、Mihara Shoko、Niwa Tatsuya、Taguchi Hideki、Nomata Jiro、Wakabayashi Ken-ichi、Hisabori Toru
  • Journal Title: Plant and Cell Physiology Volume: in press Issue: 7 Pages: 1-10
  • DOI: 10.1093/pcp/pcz056
  • Peer Reviewed
• [Journal Article] Translation‐coupled protein folding assay using a protease to monitor the folding status (2019)
  • Author(s): Niwa Tatsuya、Uemura Eri、Matsuno Yuki、Taguchi Hideki
  • Journal Title: Protein Science Volume: 28 Issue: 7 Pages: 1252-1261
  • DOI: 10.1002/pro.3624
  • Peer Reviewed
• [Journal Article] Large-scale analysis of diffusional dynamics of proteins in living yeast cells using fluorescence correlation spectroscopy (2019)
  • Author(s): Fukuda Takafumi、Kawai-Noma Shigeko、Pack Chan-Gi、Taguchi Hideki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 520 Issue: 2 Pages: 237-242
  • DOI: 10.1016/j.bbrc.2019.09.066
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Catalyst-proximity protein chemical labelling on affinity beads targeting endogenous lectins (2019)
  • Author(s): Tsushima Michihiko、Sato Shinichi、Niwa Tatsuya、Taguchi Hideki、Nakamura Hiroyuki
  • Journal Title: Chemical Communications Volume: 55 Issue: 88 Pages: 13275-13278
  • DOI: 10.1039/c9cc05231c
  • Peer Reviewed
• [Journal Article] A LEA model peptide protects the function of a red fluorescent protein in the dry state (2019)
  • Author(s): T. Furuki, T. Niwa, H. Taguchi, R. Hatanaka, T. Kikawada, M. Sakurai
  • Journal Title: Biochem. Biophys. Reports Volume: 17 Pages: 27-31
  • DOI: 10.1016/j.bbrep.2018.11.006
  • Peer Reviewed / Open Access
• [Journal Article] Large-scale aggregation analysis of eukaryotic proteins reveals an involvement of intrinsically disordered regions in protein folding. (2018)
  • Author(s): Uemura E, Niwa T, Minami S, Takemoto K, Fukuchi S, Machida K, Imataka H, Ueda T, Ota M, Taguchi H.
  • Journal Title: Sci Rep. Volume: 8 Issue: 1 Pages: 678-678
  • DOI: 10.1038/s41598-017-18977-5
  • Peer Reviewed / Open Access
• [Journal Article] Electrostatic interactions between middle domain motif-1 and the AAA1 module of the bacterial ClpB chaperone are essential for protein disaggregation (2018)
  • Author(s): Sugita Saori、Watanabe Kumiko、Hashimoto Kana、Niwa Tatsuya、Uemura Eri、Taguchi Hideki、Watanabe Yo-hei
  • Journal Title: Journal of Biological Chemistry Volume: 293 Issue: 50 Pages: 19228-19239
  • DOI: 10.1074/jbc.ra118.005496
  • Peer Reviewed / Open Access
• [Journal Article] The Absence of Thioredoxin m1 and Thioredoxin C in Anabaena sp. PCC 7120 Leads to Oxidative Stress (2018)
  • Author(s): Deschoenmaeker Frederic、Mihara Shoko、Niwa Tatsuya、Taguchi Hideki、Wakabayashi Ken-Ichi、Hisabori Toru
  • Journal Title: Plant and Cell Physiology Volume: 59 Pages: 2432-2441
  • DOI: 10.1093/pcp/pcy163
  • Peer Reviewed