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A novel mechanism of spermatogenesis regulated by long noncoding RNA and multi-functional genome element

Research Project

Project/Area Number 20H03285
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 44040:Morphology and anatomical structure-related
Research InstitutionHokkaido University

Principal Investigator

KIMURA Atsushi  北海道大学, 理学研究院, 教授 (90422005)

Co-Investigator(Kenkyū-buntansha) 佐竹 炎  公益財団法人サントリー生命科学財団, 生物有機科学研究所・統合生体分子機能研究部, 主幹研究員 (20280688)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2023: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Keywords精子形成 / 長鎖非コードRNA / ゲノム / dual promoter-enhancer / 遺伝子発現調節 / テストステロン / エピジェネティクス
Outline of Research at the Start

本研究はマウスを用いて精子形成のメカニズムを解明することを目指したものである。精子形成では減数分裂中の一次精母細胞において特に重要な遺伝子が転写活性化することが不可欠であるが、そのメカニズムは明らかではない。本研究では、ともに一次精母細胞で重要な機能を果たす長鎖非コードRNAと多機能性ゲノムdual promoter-enhancerが協働してこの転写活性化を担うという、精子形成におけるこれまでにない新しいメカニズムを明らかにする。

Outline of Final Research Achievements

An important process during spermatogenesis is meiosis, in which many functional genes are transcriptionally activated in primary spermatocytes. We revealed that the long noncoding RNA (lncRNAs) and the dual promoter-enhancer (DPE), a genome sequence possessing both promoter and enhancer activity, play roles in this transcriptional activation. In this study, we tested the hypothesis that lncRNAs and DPEs cooperatively function in gene regulation during meiosis. Genome-wide analyses identified DPEs and target genes of lncRNAs in primary spermatocytes, and as a result of comparison of those data, we suggest the cooperative contribution of DPEs and lncRNAs to the gene activation. Moreover, we also found that some lncRNAs are involved in the regulation of steroidogenesis in the testis.

Academic Significance and Societal Importance of the Research Achievements

本研究は哺乳類のゲノムにおいて大部分を占める、タンパク質を指定しない非コード領域の機能解明に貢献するものである。非コード領域は生命科学のダークマターともよばれる大きな謎であり、本研究はその機能解明に貢献する点で学術的価値がある。しかも本研究は、生命を次世代につないでいくうえで不可欠な精子をつくる過程で機能する非コード領域の研究であり、ゲノムの最も本質的な機能を明らかにすることにつながる。社会的観点からは、晩婚化が進む日本社会において男性側の問題によって不妊治療を行うケースが増えており、本研究の成果はこの社会的問題解決の糸口を見出す可能性がある。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (7 results)

All 2024 2023 2022 2021

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (3 results) (of which Invited: 2 results)

  • [Journal Article] PTBP2 binds to a testis-specific long noncoding RNA, Tesra, and activates transcription of the Prss42/Tessp-2 gene2024

    • Author(s)
      Sato Josei、Satoh Yui、Yamamoto Takehiro、Watanabe Takehiro、Matsubara Shin、Satake Honoo、Kimura Atsushi P.
    • Journal Title

      Gene

      Volume: 893 Pages: 147907-147907

    • DOI

      10.1016/j.gene.2023.147907

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evidence for a functional role of Start, a long noncoding RNA, in mouse spermatocytes2022

    • Author(s)
      Otsuka Kai、Yang Hong、Matsubara Shin、Shiraishi Akira、Kurihara Misuzu、Satake Honoo、Kimura Atsushi P.
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 8 Pages: e0273279-e0273279

    • DOI

      10.1371/journal.pone.0273279

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Testis-Specific Long Noncoding RNA, Start, Is a Regulator of Steroidogenesis in Mouse Leydig Cells2021

    • Author(s)
      Otsuka Kai、Matsubara Shin、Shiraishi Akira、Takei Natsumi、Satoh Yui、Terao Miho、Takada Shuji、Kotani Tomoya、Satake Honoo、Kimura Atsushi P.
    • Journal Title

      Frontiers in Endocrinology

      Volume: 12 Pages: 665874-665874

    • DOI

      10.3389/fendo.2021.665874

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A dual enhancer-silencer element, DES-K16, in mouse spermatocyte-derived GC-2spd(ts) cells2021

    • Author(s)
      Bandara Thusitha A.M.K.、Otsuka Kai、Matsubara Shin、Shiraishi Akira、Satake Honoo、Kimura Atsushi P.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 534 Pages: 1007-1012

    • DOI

      10.1016/j.bbrc.2020.10.049

    • NAID

      120007181810

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] マウス精巣特異的長鎖非コードRNAの転写活性化におけるPTBP2タンパク質の寄与2023

    • Author(s)
      佐藤丈生、佐藤優衣、山本雄広、渡辺健宏、松原伸、佐竹炎、木村敦
    • Organizer
      第47回日本比較内分泌学会大会及びシンポジウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] マウス精巣長鎖非コードRNAの意義を求めて2022

    • Author(s)
      木村敦
    • Organizer
      第8回生殖若手の会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] マウス精子形成における長鎖非コードRNAの機能と作用機構2022

    • Author(s)
      木村敦
    • Organizer
      第46回日本比較内分泌学会大会
    • Related Report
      2022 Annual Research Report
    • Invited

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Published: 2020-04-28   Modified: 2025-01-30  

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