研究者業績

今高 寛晃

イマタカ ヒロアキ  (Hiroaki Imataka)

基本情報

所属
兵庫県立大学 工学研究科 教授
学位
農学博士(東京大学)

研究者番号
50201942
J-GLOBAL ID
201801002037126056
researchmap会員ID
B000310027

外部リンク

1.学歴
1979年 三重県立上野高等学校卒業
1979年 東京大学理科2類入学
1983年 東京大学農学部畜産獣医学科卒業
1985年 獣医師免許取得
1988年 東京大学大学院博士課程修了

2.職歴
1988年 東北大学理学部 ポスドク
1990年 京都大学ウイルス研究所ポスドク
1994年 McGill大学医学部 研究員
2002年 理化学研究所 研究員
2008年 兵庫県立大学大学院工学研究科 教授

論文

 90
  • Kodai Machida, Rin Tanaka, Seraya Miki, Shotaro Noseda, Mayumi Yuasa-Sunagawa, Hiroaki Imataka
    BioTechniques 76(4) 161-168 2024年4月  
    Programmed-1 ribosomal frameshifting (-1 PRF) is a translational mechanism adopted by some viruses, including SARS-CoV-2. To find a compound that can inhibit -1 PRF in SARS-CoV-2, we set up a high-throughput screening system using a HeLa cell extract-derived cell-free protein synthesis (CFPS) system. A total of 32,000 compounds were individually incubated with the CFPS system programmed with a -1 PRF-EGFP template. Several compounds were observed to decrease the -1 PRF-driven fluorescence, and one of them had some suppressive effect on -1 PRF of a SARS-CoV-2 genome sequence in transfected cells. Thus the CFPS system can be used as a tool for a high-throughput screening of chemicals.
  • Hayato Ito, Kodai Machida, Mayuka Hasumi, Morio Ueyama, Yoshitaka Nagai, Hiroaki Imataka, Hideki Taguchi
    Scientific reports 13(1) 22826-22826 2023年12月20日  
    Nucleotide repeat expansion of GGGGCC (G4C2) in the non-coding region of C9orf72 is the most common genetic cause underlying amyotrophic lateral sclerosis and frontotemporal dementia. Transcripts harboring this repeat expansion undergo the translation of dipeptide repeats via a non-canonical process known as repeat-associated non-AUG (RAN) translation. In order to ascertain the essential components required for RAN translation, we successfully recapitulated G4C2-RAN translation using an in vitro reconstituted translation system comprising human factors, namely the human PURE system. Our findings conclusively demonstrate that the presence of fundamental translation factors is sufficient to mediate the elongation from the G4C2 repeat. Furthermore, the initiation mechanism proceeded in a 5' cap-dependent manner, independent of eIF2A or eIF2D. In contrast to cell lysate-mediated RAN translation, where longer G4C2 repeats enhanced translation, we discovered that the expansion of the G4C2 repeats inhibited translation elongation using the human PURE system. These results suggest that the repeat RNA itself functions as a repressor of RAN translation. Taken together, our utilization of a reconstituted RAN translation system employing minimal factors represents a distinctive and potent approach for elucidating the intricacies underlying RAN translation mechanism.
  • Akihiro Kimura, Takeshi Takagi, Thiprampai Thamamongood, Satoshi Sakamoto, Takumi Ito, Iwao Seki, Masahiro Okamoto, Hiroyuki Aono, Satoshi Serada, Tetsuji Naka, Hiroaki Imataka, Kensuke Miyake, Takuya Ueda, Miki Miyanokoshi, Keisuke Wakasugi, Noriko Iwamoto, Norio Ohmagari, Takahiro Iguchi, Takeshi Nitta, Hiroshi Takayanagi, Hiroyuki Yamashita, Hiroshi Kaneko, Haruka Tsuchiya, Keishi Fujio, Hiroshi Handa, Harumi Suzuki
    Annals of the rheumatic diseases 82(9) 1153-1161 2023年9月  
    OBJECTIVES: Recent studies demonstrate that extracellular-released aminoacyl-tRNA synthetases (aaRSs) play unique roles in immune responses and diseases. This study aimed to understand the role of extracellular aaRSs in the pathogenesis of rheumatoid arthritis (RA). METHODS: Primary macrophages and fibroblast-like synoviocytes were cultured with aaRSs. aaRS-induced cytokine production including IL-6 and TNF-α was detected by ELISA. Transcriptomic features of aaRS-stimulated macrophages were examined using RNA-sequencing. Serum and synovial fluid (SF) aaRS levels in patients with RA were assessed using ELISA. Peptidyl arginine deiminase (PAD) 4 release from macrophages stimulated with aaRSs was detected by ELISA. Citrullination of aaRSs by themselves was examined by immunoprecipitation and western blotting. Furthermore, aaRS inhibitory peptides were used for inhibition of arthritis in two mouse RA models, collagen-induced arthritis and collagen antibody-induced arthritis. RESULTS: All 20 aaRSs functioned as alarmin; they induced pro-inflammatory cytokines through the CD14-MD2-TLR4 axis. Stimulation of macrophages with aaRSs displayed persistent innate inflammatory responses. Serum and SF levels of many aaRSs increased in patients with RA compared with control subjects. Furthermore, aaRSs released PAD4 from living macrophages, leading to their citrullination. We demonstrate that aaRS inhibitory peptides suppress cytokine production and PAD4 release by aaRSs and alleviate arthritic symptoms in a mouse RA model. CONCLUSIONS: Our findings uncovered the significant role of aaRSs as a novel alarmin in RA pathogenesis, indicating that their blocking agents are potent antirheumatic drugs.
  • Yosuke Ito, Yuhei Chadani, Tatsuya Niwa, Ayako Yamakawa, Kodai Machida, Hiroaki Imataka, Hideki Taguchi
    Nature communications 13(1) 7451-7451 2022年12月2日  
    Robust translation elongation of any given amino acid sequence is required to shape proteomes. Nevertheless, nascent peptides occasionally destabilize ribosomes, since consecutive negatively charged residues in bacterial nascent chains can stochastically induce discontinuation of translation, in a phenomenon termed intrinsic ribosome destabilization (IRD). Here, using budding yeast and a human factor-based reconstituted translation system, we show that IRD also occurs in eukaryotic translation. Nascent chains enriched in aspartic acid (D) or glutamic acid (E) in their N-terminal regions alter canonical ribosome dynamics, stochastically aborting translation. Although eukaryotic ribosomes are more robust to ensure uninterrupted translation, we find many endogenous D/E-rich peptidyl-tRNAs in the N-terminal regions in cells lacking a peptidyl-tRNA hydrolase, indicating that the translation of the N-terminal D/E-rich sequences poses an inherent risk of failure. Indeed, a bioinformatics analysis reveals that the N-terminal regions of ORFs lack D/E enrichment, implying that the translation defect partly restricts the overall amino acid usage in proteomes.
  • Kodai Machida, Shoma Miyawaki, Kuru Kanzawa, Taiki Hakushi, Tomonori Nakai, Hiroaki Imataka
    ACS synthetic biology 10(11) 3158-3166 2021年11月19日  
    In vitro reconstitution of whole cellular events is one of the important goals in synthetic biology. Using a cell-free protein synthesis (CFPS) system reconstituted with human translation factors and chaperones, we reproduced the biogenesis of β-actin, synthesis, folding, and polymerization in a test tube. This system enabled us to define which step of the β-actin biogenesis was defective in genetic mutations related to diseases. Hence, the CFPS system reconstituted with human factors may be a useful tool for analyzing proteostasis in eukaryotes.

MISC

 7

講演・口頭発表等

 12

共同研究・競争的資金等の研究課題

 19