Maintenance of the germ cell genome by non-coding RNA

• Project/Area Number: 17K08644
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Keio University
• Principal Investigator: MURANO Kensaku 慶應義塾大学, 医学部(信濃町), 講師 (80535295)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: トランスポゾン / 小分子RNA / PIWI / 転写 / 生殖 / ヘテロクロマチン / 転写抑制 / small RNA / サイレンシング / 生殖細胞 / アルゴノート / ゲノム医科学

Outline of Final Research Achievements

Retrotransposons, which repeatedly proliferate in the germline genome, are a threat to the next generation of inheritance of life. A complex of non-coding small molecule RNAs (piRNAs) and PIWI proteins represses retrotransposons to maintain genomic homeostasis. This study has shown that the newly identified nuclear export factor 2 (Nxf2) represses the transcription of transposons through its interaction with Piwi-piRNA complex.

Academic Significance and Societal Importance of the Research Achievements

ショウジョウバエ個体の解析結果から、Nxf2がPiwiと同様に不妊の原因遺伝子であった。詳細な分子メカニズムの解析により、Piwi-piRNA経路によるトランスポゾンの抑制機構は少なくとも二段階からなることがわかった。すなわち、Nxf2-Panx複合体はヘテロクロマチンを形成する前に、トランスポゾンの転写反応を抑制することが明らかとなった。マウスを用いた解析からNxf2は精巣の発達に重要であることを踏まえると、同じ哺乳類であるヒトの生殖においても、トランスポゾンを抑制することが重要であることを示唆している。

Research Products

• [Journal Article] Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing (2019)
  • Author(s): Murano, K., Iwasaki Y.W., Ishizu H., Mashiko, A., Shibuya, A., Kondo, S., Adachi, S., Suzuki, S., Saito, K., Natsume, T., Siomi, M.C., Siomi, H.
  • Journal Title: The EMBO Journal Volume: 印刷中 Issue: 17 Pages: 1-20
  • DOI: 10.15252/embj.2019102870
  • Peer Reviewed / Open Access
• [Journal Article] Essential roles of Windei and nuclear monoubiquitination of Eggless/ SETDB 1 in transposon silencing (2019)
  • Author(s): Osumi Ken、Sato Kaoru、Murano Kensaku、Siomi Haruhiko、Siomi Mikiko C
  • Journal Title: EMBO reports Volume: 20 Issue: 12
  • DOI: 10.15252/embr.201948296
  • Peer Reviewed / Open Access
• [Journal Article] Template Activating Factor-I α Regulates Retroviral Silencing during Reprogramming (2019)
  • Author(s): Bui Phuong Linh、Nishimura Ken、Seminario Mondejar Gonzalo、Kumar Arun、Aizawa Shiho、Murano Kensaku、Nagata Kyosuke、Hayashi Yohei、Fukuda Aya、Onuma Yasuko、Ito Yuzuru、Nakanishi Mahito、Hisatake Koji
  • Journal Title: Cell Reports Volume: 29 Issue: 7 Pages: 1909-1922
  • DOI: 10.1016/j.celrep.2019.10.010
  • NAID: 120007127699
  • Peer Reviewed / Open Access
• [Journal Article] Tbx6 Induces Nascent Mesoderm from Pluripotent Stem Cells and Temporally Controls Cardiac versus Somite Lineage Diversification. (2018)
  • Author(s): Sadahiro T, Isomi M, Muraoka N, Kojima H, Haginiwa S, Kurotsu S, Tamura F, Tani H, Tohyama S, Fujita J, Miyoshi H, Kawamura Y, Goshima N, Iwasaki YW, Murano K, Saito K, Oda M, Andersen P, Kwon C, Uosaki H, Nishizono H, Fukuda K, Ieda M
  • Journal Title: Cell stem cell Volume: 23(3) Issue: 3 Pages: 382-395
  • DOI: 10.1016/j.stem.2018.07.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Profiling Open Chromatin Structure in the Ovarian Somatic Cells Using ATAC-seq (2018)
  • Author(s): Murano K, Iwasaki YW, Siomi H.
  • Journal Title: Methods in Molecluar Biology Volume: 1680 Pages: 165-177
  • DOI: 10.1007/978-1-4939-7339-2_11
  • ISBN: 9781493973385, 9781493973392
  • Peer Reviewed
• [Journal Article] Mitotic phosphorylation of CCCTC-binding factor (CTCF) reduces its DNA binding activity (2017)
  • Author(s): Sekiya T, Murano K, Kato K, Kawaguchi A, Nagata K
  • Journal Title: FEBS Open Bio Volume: 7 Pages: 397-404
  • NAID: 120007129136
  • Peer Reviewed
• [Presentation] Piwi-piRNA silencing is triggered by Nxf2-mediated transcriptional regulation prior to heterochromatin formation (2019)
  • Author(s): 村野健作
  • Organizer: 第42回日本分子生物学会
• [Presentation] Nuclear RNA export factor variant initiates Piwi-piRNA-guided co-transcriptional silencing (2019)
  • Author(s): 村野健作
  • Organizer: 第21回日本RNA学会年会
• [Presentation] Nuclear RNA export factor variant triggers Piwi-piRNA-mediated co-transcriptional silencing (2019)
  • Author(s): Murano K
  • Organizer: RNA 2019 (Poland)
• [Presentation] Nuclear RNA export factor variant triggers Piwi-piRNA-mediated co-transcriptional silencing (2019)
  • Author(s): Murano K
  • Organizer: Keystone symposia "Small Regulatory RNAs" (Korea)
• [Presentation] Nuclear RNA export factor variant triggers Piwi-piRNA-mediated co-transcriptional silencing (2019)
  • Author(s): Kensaku Murano, Yuka W. Iwasaki, Akane Mashiko, Haruhiko Siomi
  • Organizer: The 20th Takeda Science Foundation Symposium on BioSciences
  • Int'l Joint Research
• [Presentation] Piwi-piRNA silencing is triggered by Nxf2-mediated transcriptonal regulation prior to heterochromatin formation (2018)
  • Author(s): 岩崎由香、村野健作、益子あかね、渋谷あおい、塩見春彦
  • Organizer: 第20回日本RNA学会年会
• [Presentation] Piwi-piRNAによるトランスポゾン抑制はNxf2を介した転写制御とヘテロクロマチン形成により引き起こされる (2018)
  • Author(s): 村野健作、岩崎由香、益子あかね、渋谷あおい、塩見春彦
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] MuERV-L Gagタンパク質と相互作用するRNAの探索 (2018)
  • Author(s): 村野健作
  • Organizer: 転写因子研究会
• [Presentation] Essential function of Panoramix/Scilencio-Nxf2 complex in the Drosophila Piwi-piRNA pathway (2017)
  • Author(s): 村野健作, 岩崎由香, 益子あかね, 塩見春彦
  • Organizer: 2017年度生命科学系合同年次大会
• [Presentation] Essential function of Panoramix/Scilencio-Nxf2 complex in the Drosophila Piwi-piRNA pathway (2017)
  • Author(s): 村野健作, 岩崎由香, 益子あかね, 塩見春彦
  • Organizer: 第19回日本RNA学会年会
• [Remarks] Siomi Lab
  • URL: http://siomilab.med.keio.ac.jp