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Identification and function of endogenous retrovirus derived genes that mediate cell fusion

Research Project

Project/Area Number 17K19359
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Molecular and Genome biology and related fields
Research InstitutionTokai University

Principal Investigator

UEDA Mahoko  東海大学, 医学部, 奨励研究員 (60760353)

Co-Investigator(Kenkyū-buntansha) 三橋 里美  横浜市立大学, 医学部, 助教 (40466222)
Project Period (FY) 2017-06-30 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
KeywordsEndogenous retrovirus / envelope gene / cell differentiation / cell fusion / novel gene / レトロトランスポゾン / ERV / 新規遺伝子 / 細胞融合 / 筋細胞 / 系統特異性 / RNA-seq解析 / トランスポゾン / RNA-seq / 性差 / myoblast / osteoblast / 細胞分化 / 破骨細胞 / 内在性レトロウイルス / 分化 / 遺伝子発現
Outline of Final Research Achievements

The purpose of this study is to identify novel genes that directly mediate cell fusion during myoblast and osteoclast differentiation. In these cells, the mutual fusion is indispensable for normal cell differentiation, however the gene that mediate the fusion and the fusion mechanism are unclear. To identify such novel genes, we focused on an envelope domain of endogenous retroviruses (ERV), which have the potential to mediate cell fusion, in mammalian genomes. First, we performed RNA-seq analyses and identified candidates for the envelope-derived genes in mice myoblasts and osteoclasts. After further filtering using protein structures predicted based on candidate sequences, we obtained final candidate sets. Then, we performed siRNA knockdown and over-expression analyses and identified a sequence that showed fusion activity in myoblasts. We are now in the final stage of this project, and confirming the function of the candidates.

Academic Significance and Societal Importance of the Research Achievements

本研究は、分化時の融合細胞で多くの発現解析が行われてきたにも関わらず発見されていない、細胞融合にかかわる直接因子の特定を目指したものである。本研究により、ERV由来の遺伝子が筋細胞・破骨細胞の分化融合にかかわることが明らかになれば、広く細胞融合という現象が、機能の無いと思われてきたゲノム領域にある、外来性の遺伝子により媒介されることを示すことになり、進化遺伝学やゲノム科学の分野に新しい知見をもたらすと考えられる。また今後、ヒトの筋細胞・破骨細胞の分化・融合メカニズムが解明されれば、発症機序が不明な筋再生や骨代謝疾患の治療開発に道を開くことも期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017

All Journal Article (1 results) (of which Open Access: 1 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Comprehensive genomic analysis reveals dynamic evolution of mammalian transposable elements that code for viral-like protein domains2019

    • Author(s)
      Mahoko T. Ueda, Kirill Kryukov, Satomi Mitsuhashi, Hiroaki Mitsuhashi, Tadashi Imanishi, So Nakagawa
    • Journal Title

      bioRxiv

      Volume: NA Pages: 1-46

    • DOI

      10.1101/628875

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Open Access
  • [Presentation] 哺乳類ゲノムに存在するレトロウイルス様タンパク質をコードする配列の比較ゲノム進化解析2019

    • Author(s)
      中川草、上田真保子
    • Organizer
      第42回 日本分子生物学会年会 (MBSJ2019)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 哺乳類ゲノムのレトロトランスポゾンに由来するタンパク質コード配列のダイナミックな進化2019

    • Author(s)
      上田真保子,クリュコフ キリル,三橋里美,三橋弘明,今西規,中川草
    • Organizer
      日本進化学会第21回大会シンポジウム“大規模DNAシーケンス時代のウイルス進化研究”
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Genome-wide comparative analysis of mammalian transposable elements that code for viral-like proteins.2019

    • Author(s)
      1Ueda MT, Mitsuhashi S, Mitsuhashi H, Imanishi T, Nakagawa S
    • Organizer
      The Society for Molecular Biology and Evolution (SMBE2019), Symposia “Repeats and mobile elements as drivers of innovations in protein coding genes”
    • Related Report
      2019 Annual Research Report
  • [Presentation] gEVE database provides possibly protein-coding sequences that are similar to viruses in 20  mammalian genomes2019

    • Author(s)
      Nakagawa S, Ueda MT
    • Organizer
      3rd Annual Meeting of the EVBC, Glasgow
    • Related Report
      2019 Annual Research Report
  • [Presentation] Genome-wide comparative analysis of mammalian transposable elements that code for proteins2019

    • Author(s)
      Mahoko Ueda
    • Organizer
      Society of Molecular Biology and Evolution 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genome-wide comparative analysis of mammalian transposable elements that code for proteins2018

    • Author(s)
      上田真保子
    • Organizer
      第41回日本分子生物学会年会・生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2018 Research-status Report
  • [Presentation] 哺乳類のトランスポゾンに由来するタンパク質コード配列の比較ゲノム解析2018

    • Author(s)
      上田真保子
    • Organizer
      日本遺伝学会第90回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 哺乳類のトランスポゾンに由来するタンパク質コード配列の比較ゲノム解析2018

    • Author(s)
      上田真保子
    • Organizer
      2018年度遺伝研研究会 転移因子と宿主の相互作用による生命機能と進化
    • Related Report
      2018 Research-status Report
  • [Presentation] Transcriptome analysis to identify genes derived from endogenous retrovirus that mediate cell-cell fusion during myoblast differentiation2018

    • Author(s)
      Mahoko Ueda
    • Organizer
      Society of Molecular Biology and Evolution 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Transcriptome analysis to identify genes derived from endogenous retrovirus that mediate cell-cell fusion during myoblast differentiation2018

    • Author(s)
      Mahoko Ueda
    • Organizer
      SMBE 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細胞融合にかかわる内在性レトロウイルス由来遺伝子の同定2017

    • Author(s)
      上田真保子
    • Organizer
      第41回日本分子生物学会年会・生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2021-02-19  

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