Germline genome integrity maintained by small RNA-mediated chromatin regulation

• Project/Area Number: 18H02421
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Keio University
• Principal Investigator: IWASAKI Yuka 慶應義塾大学, 医学部(信濃町), 准教授 (80612647)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 転写制御 / エピゲノム制御 / ゲノム高次構造 / 非コードRNA / RNAサイレンシング / 小分子RNA / 生殖組織 / 不妊 / トランスポゾン / 卵巣 / 転移因子 / 遺伝子発言調節 / ゲノム安定性 / クロマチン因子 / RNA結合タンパク質 / 遺伝子発現調節

Outline of Final Research Achievements

PIWI-interacting RNAs (piRNAs) are germline-specific small RNAs that form effector complexes with PIWI proteins to preserve genomic integrity by repressing transposable elements. Using both cultured cell line system and Drosophila mutants, we showed that Piwi-piRNA complexes promote epigenetic and chromatin architectural changes, leading to the sterility phenotype.

Academic Significance and Societal Importance of the Research Achievements

本研究では、Piwi-piRNA複合体はトランスポゾンの発現を抑制する際にダイナミックなクロマチン高次構造変化を伴うことを明らかにした。このことから、PIWI-piRNAによるトランスポゾンの転移抑制が不妊を回避するために必要であろうという従来のモデルに対し、PIWI-piRNA複合体が誘導するクロマチン構造がトランスポゾンの抑制と不妊の回避の両方に必須の役割を果たしている可能性を示唆することができた。これは将来的に不妊症が引き起こされる機構の科学的説明などにつながる知見であると考えている。

Research Products

• [Journal Article] Hamster PIWI proteins bind to piRNAs with stage-specific size variations during oocyte maturation (2021)
  • Author(s): Ishino Kyoko、Hasuwa Hidetoshi、Yoshimura Jun、Iwasaki Yuka W、Nishihara Hidenori、Seki Naomi M、Hirano Takamasa、Tsuchiya Marie、Ishizaki Hinako、Masuda Harumi、Kuramoto Tae、Saito Kuniaki、Sakakibara Yasubumi、Toyoda Atsushi、Itoh Takehiko、Siomi Mikiko C、Morishita Shinichi、Siomi Haruhiko
  • Journal Title: Nucleic Acids Research Volume: 49 Issue: 5 Pages: 2700-2720
  • DOI: 10.1093/nar/gkab059
  • Peer Reviewed / Open Access
• [Journal Article] Production of functional oocytes requires maternally expressed PIWI genes and piRNAs in golden hamsters (2021)
  • Author(s): Hasuwa Hidetoshi、Iwasaki Yuka W.、Wan Kin Au Yeung、Ishino Kyoko、Masuda Harumi、Sasaki Hiroyuki、Siomi Haruhiko
  • Journal Title: bioRxiv Volume: -
  • DOI: 10.1101/2021.01.27.428354
  • Open Access
• [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] 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: bioRxiv Volume: -
  • DOI: 10.1101/605725
  • 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
• [Presentation] Piwi-piRNA mediated silencing induces step-wise nuclear architectural changes (2021)
  • Author(s): Yuka W. Iwasaki
  • Organizer: JSDB/APDBN Symposium, Virtual conference
  • Int'l Joint Research / Invited
• [Presentation] Nuclear architectural changes during the establishment of Piwi-piRNA mediated silencing (2020)
  • Author(s): Yuka W. Iwasaki
  • Organizer: 第43回日本分子生物学会年会
  • Invited
• [Presentation] Regulation of non-coding genome: Transposable element silencing by PIWI-piRNAs (2020)
  • Author(s): Yuka W. Iwasaki
  • Organizer: ASMI BioInfo Summer 2020
  • Int'l Joint Research / Invited
• [Presentation] Impact of Piwi-piRNA mediated transcriptional silencing on nuclear architecture in Drosophila (2019)
  • Author(s): Yuka W. Iwasaki
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Piwi-piRNA silencing-coupled changes of nuclear architecture in Drosophila (2019)
  • Author(s): Yuka W. Iwasaki
  • Organizer: 第21回日本RNA学会年会
• [Presentation] ショウジョウバエPiwi-piRNAが制御する核内高次構造 (2019)
  • Author(s): 岩崎由香，塩見春彦
  • Organizer: RNAi研究会年会
• [Presentation] Piwi-piRNA silencing-coupled changes of nuclear architecture in Drosophila (2019)
  • Author(s): Yuka W. Iwasaki
  • Organizer: International Symposium for Female Researchers in Chromatin Biology
  • Int'l Joint Research
• [Presentation] Piwi-piRNA silencing-coupled changes of nuclear architecture in Drosophila (2019)
  • Author(s): Yuka W. Iwasaki, Haruhiko Siomi
  • Organizer: 14th Asia Epigenome Meeting (AEM) / 3rd Taipei Epigenetics and Chromatin Meeting
  • Int'l Joint Research
• [Presentation] Piwi-piRNA silencing-coupled changes of nuclear architecture in Drosophila (2019)
  • Author(s): Yuka W. Iwasaki, Haruhiko Siomi
  • Organizer: Keystone Symposia: Small Regulatory RNAs
  • Int'l Joint Research
• [Presentation] Piwi-piRNA silencing-coupled changes of nuclear architecture in Drosophila (2019)
  • Author(s): Yuka W. Iwasaki
  • Organizer: RNAフロンティアミーティング2019
• [Presentation] Piwi-piRNA silencing-coupled changes of nuclear architecture in Drosophila (2019)
  • Author(s): Yuka W. Iwasaki, Haruhiko Siomi
  • Organizer: Keystone Symposia Conference - Small Regulatory RNAs
  • Int'l Joint Research
• [Presentation] Piwi-piRNA silencing-coupled changes of nuclear architecture in Drosophila (2018)
  • Author(s): Yuka W. Iwasaki, Haruhiko Siomi
  • Organizer: The 20th Takeda Science Foundation Symposium on Bioscience - RNA Neobiology
  • Int'l Joint Research
• [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): 岩崎由香
  • Organizer: 転移因子研究会 2018
• [Presentation] Nuclear RNA export factor variant triggers Piwi-piRNA-mediated co-transcriptional silencing (2018)
  • Author(s): Yuka W. Iwasaki
  • Organizer: 2nd JAJ (Joint Australia-Japan/Japan-Australia Joint) RNA meeting
• [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): 岩崎由香、村野健作、益子あかね、渋谷あおい、塩見春彦
  • Organizer: 日本RNA学会年会
• [Presentation] Piwi-piRNA silencing is triggered by Nxf2 mediated transcriptional 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: 第二回慶應ライフサイエンスシンポジウム