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Elucidation for chaperone RNAs that prevent protein aggregation associated with neurodegenerative diseases.

Research Project

Project/Area Number 18K06201
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionHokkaido University

Principal Investigator

Kitamura Akira  北海道大学, 先端生命科学研究院, 講師 (10580152)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsタンパク質恒常性 / タンパク質凝集体 / 神経変性疾患 / 筋萎縮性側索硬化症 / RNA / 分子シャペロン / ALS / TDP-43 / 蛍光相関分光法 / 線虫 / CD / FRAP / FCCS / RNA-タンパク質相互作用 / リコンビナントタンパク質 / タンパク質凝集 / 蛍光測定
Outline of Final Research Achievements

Protein aggregates are frequently observed in neurons from neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). In addition, various studies have suggested that protein aggregates may be responsible for neuronal cell death. In this study, we showed that an aggregate-prone protein, which is the cause of ALS, directly interacts with RNA using fluorescence cross-correlation spectroscopy (FCCS), an interaction analysis technique with single-molecule sensitivity. Furthermore, we demonstrated that the intracellular expression of the RNA prevents aggregate formation.

Academic Significance and Societal Importance of the Research Achievements

これまでタンパク質の凝集形成を抑制する細胞内在性因子として,分子シャペロンが知られていた.分子シャペロンはタンパク質の一群である.本研究は,RNAがタンパク質凝集を直接抑制する効果を新規に実証したものである.また,このようなRNAは将来的にALSなどの治療医薬品として開発対象になりうる.本研究はその応用につながる道筋を拓いたものである.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (33 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (17 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 15 results,  Open Access: 9 results) Presentation (13 results) (of which Int'l Joint Research: 6 results,  Invited: 5 results) Remarks (1 results)

  • [Int'l Joint Research] Tata Institute of Fundamental Research(インド)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Northwestern University/Department of Molecular Biosciences/Prof. Richard Morimoto(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] ALSにおけるTDP-43タンパク質凝集体形成と遺伝子治療2021

    • Author(s)
      北村朗
    • Journal Title

      Bio Clinica

      Volume: 36 Pages: 453-456

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Detection of protein aggregation using fluorescence correlation spectroscopy.2021

    • Author(s)
      Kitamura Akira, Fujimoto Ai, Kinjo Masakata
    • Journal Title

      Journal of Visualized Experiments

      Volume: 170 Issue: 170

    • DOI

      10.3791/62576

    • NAID

      120007097384

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of the triplet-state kinetics of a photosensitizer for photoimmunotherapy by fluorescence correlation spectroscopy2021

    • Author(s)
      Takakura Hideo、Goto Yuto、Kitamura Akira、Yoshihara Toshitada、Tobita Seiji、Kinjo Masataka、Ogawa Mikako
    • Journal Title

      Journal of Photochemistry and Photobiology A: Chemistry

      Volume: 408 Pages: 113094-113094

    • DOI

      10.1016/j.jphotochem.2020.113094

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular basis of functional exchangeability between ezrin and other actin-membrane associated proteins during cytokinesis2021

    • Author(s)
      Yang Guang、Hiruma Shota、Kitamura Akira、Kinjo Masataka、Mishra Mithilesh、Uehara Ryota
    • Journal Title

      Experimental Cell Research

      Volume: 403 Issue: 2 Pages: 112600-112600

    • DOI

      10.1016/j.yexcr.2021.112600

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Spatial Image Correlation Spectroscopy (ICS): A Technique for Average Size Determination of Subcellular Accumulated Structures from Fluorescence Microscopic Images2020

    • Author(s)
      Kitamura Akira、Kinjo Masakata
    • Journal Title

      BIO-PROTOCOL

      Volume: 10 Issue: 10

    • DOI

      10.21769/bioprotoc.3624

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ALSにおけるタンパク質凝集体と遺伝子治療2020

    • Author(s)
      北村朗
    • Journal Title

      メディカル・サイエンス・ダイジェスト (MSD)

      Volume: 46 Pages: 763-765

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Membrane Surface Modulates Slow Diffusion in Small Crowded Droplets2020

    • Author(s)
      Harusawa Kanae、Watanabe Chiho、Kobori Yuta、Tomita Kazuho、Kitamura Akira、Kinjo Masataka、Yanagisawa Miho
    • Journal Title

      Langmuir

      Volume: 37 Issue: 1 Pages: 437-444

    • DOI

      10.1021/acs.langmuir.0c03086

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Session 2SHP report - decoding intracellular architecture using visualizing device development and mathematical modeling2020

    • Author(s)
      Kitamura A., Kabayama K.
    • Journal Title

      Biophysical Reviews

      Volume: x Issue: 2 Pages: 1-2

    • DOI

      10.1007/s12551-020-00641-4

    • NAID

      120007000859

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization of Intracellular Crowding Environments with Topology-Based DNA Quadruplex Sensors2019

    • Author(s)
      Takahashi Shuntaro、Yamamoto Johtaro、Kitamura Akira、Kinjo Masataka、Sugimoto Naoki
    • Journal Title

      Analytical Chemistry

      Volume: 91 Issue: 4 Pages: 2586-2590

    • DOI

      10.1021/acs.analchem.8b04177

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The AAA+ ATPase/ubiquitin ligase mysterin stabilizes cytoplasmic lipid droplets2019

    • Author(s)
      Munechika Sugihara, Daisuke Morito, Shiori Ainuki, Yoshinobu Hirano, Kazutoyo Ogino, Akira Kitamura, Hiromi Hirata, Kazuhiro Nagata
    • Journal Title

      Journal of Cell Biology

      Volume: 218 Issue: 3 Pages: 949-960

    • DOI

      10.1083/jcb.201712120

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Encapsulation of biomacromolecules by soaking and co-crystallization into porous protein crystals of hemocyanin2019

    • Author(s)
      Tsubasa Hashimoto, Yuxin Ye, Asuka Matsuno, Yuki Ohnishi, Akira Kitamura, Masataka Kinjo, Satoshi Abe, Takafumi Uenod, Min Yao, Tomohisa Ogawa, Takashi Matsuia, Yoshikazu Tanaka
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 509 Issue: 2 Pages: 577-584

    • DOI

      10.1016/j.bbrc.2018.12.096

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 蛍光相関分光の発展と応用,その最新動向2019

    • Author(s)
      山本条太郎,北村朗,金城政孝
    • Journal Title

      生物物理

      Volume: 印刷中

    • NAID

      130007653211

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TDP-43 depletion: mechanism of neuronal cell death in ALS2018

    • Author(s)
      Akira Kitamura
    • Journal Title

      Future Neurology

      Volume: 13 Issue: 3 Pages: 143-149

    • DOI

      10.2217/fnl-2018-0010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Analysis of the substrate recognition state of TDP-43 to single-stranded DNA using fluorescence correlation spectroscopy2018

    • Author(s)
      Akira Kitamura, Ai Shibasaki, Kayo Takeda, Ryoji Suno, Masataka Kinjo
    • Journal Title

      Biochem. Biophys. Reports

      Volume: 14 Pages: 58-63

    • DOI

      10.1016/j.bbrep.2018.03.009

    • NAID

      120006491827

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Determination of cytoplasmic optineurin foci sizes using image correlation spectroscopy2018

    • Author(s)
      Akira Kitamura, Hiroki Shimizu, Masataka Kinjo
    • Journal Title

      The Journal of Biochemistry

      Volume: 164 Issue: 3 Pages: 223-229

    • DOI

      10.1093/jb/mvy044

    • NAID

      120006716318

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular chaperone HSP70 prevents formation of inclusion bodies of the 25-kDa C-terminal fragment of TDP-43 by preventing aggregate accumulation2018

    • Author(s)
      Akira Kitamura, Nodoka Iwasaki, Masataka Kinjo
    • Journal Title

      Cell Stress and Chaperones

      Volume: 23 Issue: 6 Pages: 1177-1183

    • DOI

      10.1007/s12192-018-0930-1

    • NAID

      120006734164

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] The cytoplasmic region of the amyloid β‐protein precursor (APP) is necessary and sufficient for the enhanced fast velocity of APP transport by kinesin‐12018

    • Author(s)
      Maoko Tsukamoto Kyoko Chiba Yuriko Sobu Yuzuha Shiraki Yuka Okumura Saori Hata Akira Kitamura Tadashi Nakaya Seiichi Uchida Masataka Kinjo Hidenori Taru Toshiharu Suzuki
    • Journal Title

      FEBS Letters

      Volume: 592 Issue: 16 Pages: 2716-2724

    • DOI

      10.1002/1873-3468.13204

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Interaction analysis of aggregate-prone protein TDP25 and RNA in amyotrophic lateral sclerosis (ALS)2021

    • Author(s)
      藤本 愛, 金城 政孝, 北村 朗
    • Organizer
      北大細胞生物研究集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Lifespan and motility analysis of C. elegans expressing C-terminal fragments of ALS-causative TDP-432021

    • Author(s)
      Yidan Lyu, Rei Kawashima, Renee; Brielman, Richard I. Morimoto, Masataka Kinjo, Akira Kitamura
    • Organizer
      RIKEN BDP Symposium
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Aggregation process of carboxyl terminal fragments of TDP-43 protein2020

    • Author(s)
      Akira Kitamura, Masataka Kinjo
    • Organizer
      Cold Spring Harbor Laboratory 2020 Meeting "Protein homeostasis in Health & Disease"
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 蛍光相関分光法による蛍光分子光物理反応速度定数の同定 -新規免疫治療薬剤の定量的開発指針の確立に向けて-2020

    • Author(s)
      北村朗,高倉栄男,後藤悠人,金城政孝,小川美香子
    • Organizer
      2020年度・光イメージン若手の会「光塾」
    • Related Report
      2020 Annual Research Report
  • [Presentation] Reading out G-quadruplex RNA structure using transient state (TRAST) of photochemical reaction of fluorophores2019

    • Author(s)
      北村朗
    • Organizer
      第57回 日本生物物理学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Aggregation process of carboxyl terminal fragments of TDP-432019

    • Author(s)
      Akira Kitamura, Kanami Moriya, Kazuho Takahashi, Rei Kawashima, Renee Brielman, Richard I. Morimoto, Masataka Kinjo
    • Organizer
      Asian Pacific Prion Symposium 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 蛍光ゆらぎを利用した光化学反応速度定数の算出とRNA構造変化の解析2019

    • Author(s)
      北村朗, Johan Tormmalm,Jerker Widengren, 金城 政孝
    • Organizer
      第10回・光塾
    • Related Report
      2019 Research-status Report
  • [Presentation] Aggregation process of carboxyl terminal fragments of TDP-432019

    • Author(s)
      Akira Kitamura, Kanami Moriya, Kazuho Takahashi, Rei Kawashima, Renee Brielman, Richard I. Morimoto, Masataka Kinjo
    • Organizer
      QBP/OCS seminar
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Elucidation for stress granule function using chromophore-assisted light inactivation (CALI)2019

    • Author(s)
      Akira Kitamura, Haruka Kawaguchi, Tsumugi Kurosaki, Masataka Kinjo
    • Organizer
      第42回 日本分子生物学会年会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 蛍光相関分光法とその応用法を用いたALS関連細胞内凝集体形成機構の解析2019

    • Author(s)
      北村朗
    • Organizer
      サントリー生命科学財団 生物有機科学研究所 生有研シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Transient state (TRAST) monitoringを用いた生細胞内RNAフォールドの解析2019

    • Author(s)
      北村朗
    • Organizer
      定量生物の会 北海道キャラバン2019
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 蛍光ゆらぎを利用した生体分子構造変化の解析2018

    • Author(s)
      北村朗
    • Organizer
      第55回 日本生化学会北海道支部例会,日本生物物理学会北海道支部合同シンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] RNA prevents ALS-linked protein aggregation2018

    • Author(s)
      Akira Kitamura
    • Organizer
      QBP/OCS seminar
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] [プレスリリース]もやもや病の責任遺伝子が脂肪代謝の制御因子であることを発見

    • URL

      https://www.hokudai.ac.jp/news/190201_pr2.pdf

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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