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Elucidation of molecular mechanisms of RNA silencing

Research Project

Project/Area Number 26291010
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Structural biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Nishimasu Hiroshi  東京大学, 大学院理学系研究科(理学部), 助教 (00467044)

Co-Investigator(Renkei-kenkyūsha) NUREKI Osamu  東京大学, 大学院理学系研究科, 教授 (10272460)
SIOMI Mikiko  東京大学, 大学院理学系研究科, 教授 (20322745)
SIOMI Haruhiko  慶應義塾大学, 医学部, 教授 (60202107)
SHIBATA Mikihiro  金沢大学, 新学術創成研究機構, 准教授 (80631027)
KODERA Noriyuki  金沢大学, 理工研究域, 准教授 (30584635)
Research Collaborator Zhang Feng  Broad Institute, Associate Professor
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords非コードRNA / CRISPR / Cas9 / Argonaute / piRNA / ゲノム編集 / RNA / 結晶構造 / Maelstrom / Crystal structure / Ribonuclease / CRISPR-Cas9
Outline of Final Research Achievements

We purified the PIWI protein from silkworm (Siwi) and determined its crystal structure. The structure revealed the molecular mechanism by which Siwi binds piRNA to protect germ cells. In addition, we determined the crystal structures of Cas9 and Cpf1 from various bacteria, thereby improving our mechanistic understanding of diverse CRISPR-Cas enzymes and paving the way for further development of new genome-editing technologies.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (24 results)

All 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 8 results,  Open Access: 7 results,  Acknowledgement Compliant: 7 results) Presentation (12 results) (of which Int'l Joint Research: 1 results,  Invited: 6 results) Remarks (2 results)

  • [Int'l Joint Research] Broad Institute/NIH(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Broad Institute of MIT and Harvard(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Structure of Cpf1 in Complex with Guide RNA and Target DNA2016

    • Author(s)
      Yamano T, Nishimasu H, Zetsche B, Hirano H, Slaymaker IM, Li Y, Fedorova I, Nakane T, Makarova KS, Koonin EV, Ishitani R, Zhang F, Nureki O
    • Journal Title

      Cell

      Volume: 165 Issue: 4 Pages: 946-962

    • DOI

      10.1016/j.cell.2016.04.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Crystal structure of silkworm PIWI-clade Argonaute Siwi bound to piRNA2016

    • Author(s)
      Matsumoto N, Nishimasu H, Sakakibara K, Nishida KM, Hirano T, Ishitani R, Siomi H, Siomi MC, Nureki O
    • Journal Title

      Cell

      Volume: 167 Issue: 2 Pages: 484-497

    • DOI

      10.1016/j.cell.2016.09.002

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Crystal Structure of the Minimal Cas9 from Campylobacter jejuni Reveals the Molecular Diversity in the CRISPR-Cas9 Systems2016

    • Author(s)
      Yamada M, Watanabe Y, Gootenberg JS, Hirano H, Ran FA, Nakane T, Ishitani R, Zhang F, Nishimasu H, Nureki O
    • Journal Title

      Mol Cell

      Volume: 65 Issue: 6 Pages: 1109-1121

    • DOI

      10.1016/j.molcel.2017.02.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Structure and Engineering of Francisella novicida Cas92016

    • Author(s)
      Hisato Hirano, Jonathan S. Gootenberg, Takuro Horii, Omar O. Abudayyeh, Mika Kimura, Takanori Nakane, Ryuichiro Ishitani, Izuho Hatada, Feng Zhang, Hiroshi Nishimasu, Osamu Nureki
    • Journal Title

      Cell

      Volume: 164 Issue: 5 Pages: 950-961

    • DOI

      10.1016/j.cell.2016.01.039

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Structural Basis for the Altered PAM Specificities of Engineered CRISPR-Cas92016

    • Author(s)
      Seiichi Hirano, Hiroshi Nishimasu, Ryuichiro Ishitani, Osamu Nureki
    • Journal Title

      Molecular Cell

      Volume: 61 Issue: 6 Pages: 886-894

    • DOI

      10.1016/j.molcel.2016.02.018

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Crystal Structure of Staphylococcus aureus Cas92015

    • Author(s)
      Hiroshi Nishimasu, Le Cong, Winston X. Yan, F. Ann Ran, Bernd Zetsche, Yinqing Li, Arisa Kurabayashi, Ryuichiro Ishitani, Feng Zhang, Osamu Nureki
    • Journal Title

      Cell

      Volume: 162 Issue: 5 Pages: 1113-1126

    • DOI

      10.1016/j.cell.2015.08.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex2015

    • Author(s)
      Konermann S*, Brigham MD*, Trevino AE, Joung J, Abudayyeh OO, Barcena C, Hsu PD, Habib N, Gootenberg JS, Nishimasu H, Nureki O, Zhang F
    • Journal Title

      Nature

      Volume: 517 Issue: 7536 Pages: 583-588

    • DOI

      10.1038/nature14136

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Crystal Structure and Activity of the Endoribonuclease Domain of the piRNA Pathway Factor Maelstrom2015

    • Author(s)
      Naoki Matsumoto, Kaoru Sato, Hiroshi Nishimasu, Yurika Namba, Kana Miyakubi, Naoshi Dohmae, Ryuichiro Ishitani, Haruhiko Siomi, Mikiko C. Siomi, Osamu Nureki
    • Journal Title

      Cell Reports

      Volume: 11 Issue: 3 Pages: 1-10

    • DOI

      10.1016/j.celrep.2015.03.030

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Crystal structure of silkworm PIWI, Siwi, in complex with piRNA2016

    • Author(s)
      Hiroshi Nishimasu, Naoki Matsumoto, Kazuhiro Sakakibara, Kazumichi Nishida, Ryuichiro Ishitani, Haruhiko Siomi, Mikiko C. Siomi, Osamu Nureki
    • Organizer
      RNA2016
    • Place of Presentation
      京都国際会館(京都府京都市)
    • Year and Date
      2016-06-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 小型CRISPR-Cas9の結晶構造2015

    • Author(s)
      西増弘志、石谷隆一郎、濡木 理
    • Organizer
      BMB2015
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] CRISPR-Cas9の結晶構造2015

    • Author(s)
      西増弘志
    • Organizer
      第53回日本生物物理学会年会
    • Place of Presentation
      金沢大学(石川県金沢市)
    • Year and Date
      2015-09-15
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Cas9-ガイド鎖RNA-標的DNAの結晶構造2014

    • Author(s)
      西増弘志
    • Organizer
      平成26年度日本結晶学会年会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2014-11-03
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Crystal structure of Cas9 in complex with guide RNA and target DNA2014

    • Author(s)
      Nishimasu H, Ran FA, Ishitani R, Zhang F, Nureki O
    • Organizer
      平成26年度日本結晶学会年会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2014-11-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cas9-ガイド鎖RNA-標的DNA三者複合体の結晶構造2014

    • Author(s)
      西増弘志
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都)
    • Year and Date
      2014-10-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] Crystal structure of Cas9 in complex with guide RNA and target DNA2014

    • Author(s)
      Nishimasu H, Ran FA, Ishitani R, Zhang F, Nureki O
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都)
    • Year and Date
      2014-10-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 立体構造から迫る酵素の作動機構2014

    • Author(s)
      西増弘志
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都)
    • Year and Date
      2014-10-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Cas9を応用した新規技術2014

    • Author(s)
      西増弘志
    • Organizer
      第14回日本蛋白質科学会年会
    • Place of Presentation
      ワークピア横浜(横浜)
    • Year and Date
      2014-06-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Crystal structure of Cas9 in complex with guide RNA and target DNA2014

    • Author(s)
      Nishimasu H, Ran FA, Ishitani R, Zhang F, Nureki O
    • Organizer
      第14回日本蛋白質科学会年会
    • Place of Presentation
      ワークピア横浜(横浜)
    • Year and Date
      2014-06-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Crystal structure of Cas9 in complex with guide RNA and target DNA2014

    • Author(s)
      Hiroshi Nishimasu
    • Organizer
      CRISPR2014
    • Place of Presentation
      Berlin (Germany)
    • Year and Date
      2014-05-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] Crystal structure of Cas9 in complex with guide RNA and target DNA2014

    • Author(s)
      西増弘志
    • Organizer
      The 14th Tokyo RNA Club
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2014-05-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Remarks] ゲノム編集のための「小さなはさみ」のかたち

    • URL

      http://www.s.u-tokyo.ac.jp/ja/press/2015/36.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] ゲノム編集のための新たな「はさみ」-立体構造にもとづくCRISPR-Cas9の改変-

    • URL

      https://www.s.u-tokyo.ac.jp/ja/press/2016/4599/

    • Related Report
      2015 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2022-02-16  

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