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TGF-beta-induced alteration of gene silencing for stem cell maintenance and differentiation

Research Project

Project/Area Number 18K06059
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43010:Molecular biology-related
Research InstitutionOsaka University

Principal Investigator

Iki Taichiro  大阪大学, 生命機能研究科, 助教 (20774011)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords精子 / microRNA / サイレンシング / シャペロン / ショウジョウバエ / 生殖細胞 / RISC / RNAサイレンシング / 精子形成 / Argonaute / 分子シャペロン / Cyclophilin 40 / miRNA / 遺伝子サイレンシング / 精巣 / 卵巣 / Dicer / 生殖幹細胞 / TGF-β/BMP / stem cell / Drosophila melanogaster / ARGONAUTE / TGF-beta
Outline of Final Research Achievements

This project identified and characterized Cyclophilin 40 (Cyp40) as a factor essential for sperm maturation processes in Drosophila melanogaster. Small non-coding RNAs including microRNA (miRNA) and short-interfering RNA (siRNA) form the effector RNA-induced silencing complex (RISC) with Argonaute (Ago) family members. RISCs direct the silencing of genes through sequence-specific recognition of complementary targets. It was found that, in the testicular germline cells, Cyp40 assists the loading of testis-specific miRNA species onto Ago2 through the physical interaction during RISC formation. These Cyp40-dependent testis-specific miRNA, including miR-316-3p, supported the organization of individualization complex formation during sperm maturation.

Academic Significance and Societal Importance of the Research Achievements

生殖細胞は精子や卵子をつくり、受精を経て次世代を紡ぐ重要な細胞です。しかしながら、生殖細胞がどのように配偶子を形成するのか、私たちの理解は進んでいません。小分子RNAと呼ばれる多様な分子が生殖細胞において遺伝子の制御を行うことは知られていましたが、小分子RNAそのものがどのように制御されるのか、よくわかっていませんでした。今回、ショウジョウバエを用いた研究において、ヒトにも発現しているCyclophilin 40(Cyp40)タンパク質が小分子RNAを制御するはたらきをもち、精子の成熟に欠かせない因子であることがわかりました。今回の発見は不妊などの疾患の解明に繋がる可能性があります。

Report

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

    (3 results)

All 2020 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Modulation of Ago2 Loading by Cyclophilin 40 Endows a Unique Repertoire of Functional miRNAs during Sperm Maturation in Drosophila2020

    • Author(s)
      Iki T, Takami M, Kai T
    • Journal Title

      Cell Reports

      Volume: 33 Issue: 6 Pages: 108380-393

    • DOI

      10.1016/j.celrep.2020.108380

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Tissue-specific regulation of RISC loading by Hsp90 cochaperone Cyclophilin 402019

    • Author(s)
      井木 太一郎
    • Organizer
      The 20th Annual Meeting of the RNA Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Hsp90 cochaperone-mediated ARGONAUTE regulation during Drosophila spermatogenesis2019

    • Author(s)
      井木 太一郎
    • Organizer
      baRNAclub
    • Related Report
      2019 Research-status Report
    • Invited

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

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