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Analyses on vesicular traffic pathways for systemic RNAi

Research Project

Project/Area Number 16H05123
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionTokyo Women's Medical University

Principal Investigator

Mitani Shohei  東京女子医科大学, 医学部, 教授 (90192757)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
KeywordsRNAi / 小胞輸送 / 線虫 / RNA干渉 / 亜鉛トランスポーター / 亜鉛 / 脂質輸送 / 亜鉛輸送担体 / リン脂質輸送担体 / トランスポーター
Outline of Final Research Achievements

We aim to understand the mechanisms of Systemic RNAi. We used a rsd-3 mutant strain as a parent, which is defective in RNAi, and screened for suppressor mutants. We found that a zip-type zinc transporter gene mutation results in the recovery of RNAi. A human homolog gene was able to rescue the mutant phenotype, suggesting specific and functional conservation.
We additionally screened for more RNAi mutants. We mutagenized animals and treated them with an RNAi clone, which kills wild-type animals. We isolated mutant strains which are resistant to the RNAi treatment. We identified mutant genes by whole genome sequencing. A small G regulatory protein and a nematode-specific protein are RNAi-resistant.

Academic Significance and Societal Importance of the Research Achievements

RNAiは線虫に限らず、ヒト培養細胞でもsiRNAの投与によって遺伝子機能阻害で頻繁に使われている必須技術である。また、近年は核酸医薬の基本的な手法としても広く認められている。RNAiに必須な酵素群や細胞内RNA結合タンパク質はかなり解明されたが、細胞内に取り込まれた二本鎖RNAが細胞内でどのような経路を辿って機能を発揮するか、どのような経路を辿って分解代謝されるのかについてはほとんど知見がない。本研究はその解明の根本的な因子を発見するに至っている。今後、核酸医療の最適化に有用な情報となると期待される。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (42 results)

All 2020 2019 2018 2017 2016 Other

All Journal Article (30 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 30 results,  Open Access: 22 results,  Acknowledgement Compliant: 1 results) Presentation (2 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (7 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Defects in CISD-1, a mitochondrial iron-sulfur protein, lower glucose level and ATP production in Caenorhabditis elegans2020

    • Author(s)
      Hsiung KC, Liu KY, Tsai TF, Yoshina S, Mitani S, Chin-Ming Tan B, Lo SJ.
    • Journal Title

      Biomed J.

      Volume: 43 Issue: 1 Pages: 32-43

    • DOI

      10.1016/j.bj.2019.07.009

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Near-Comprehensive Resequencing of Cancer-Associated Genes in Surgically Resected Metastatic Liver Tumors of Gastric Cancer2019

    • Author(s)
      Ikari Naoki、Serizawa Akiko、Mitani Shohei、Yamamoto Masakazu、Furukawa Toru
    • Journal Title

      The American Journal of Pathology

      Volume: 189 Issue: 4 Pages: 784-796

    • DOI

      10.1016/j.ajpath.2018.12.015

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenetic basis of Takenouchi-Kosaki syndrome: Electron microscopy study using platelets in patients and functional studies in a Caenorhabditis elegans model.2019

    • Author(s)
      Uehara T, Suzuki H, Okamoto N, Kondoh T, Ahmad A, O'Connor BC, Yoshina S, Mitani S, Kosaki K, Takenouchi T.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 4418-4418

    • DOI

      10.1038/s41598-019-40988-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Near-Comprehensive Resequencing of Cancer-Associated Genes in Surgically Resected Metastatic Liver Tumors of Gastric Cancer.2019

    • Author(s)
      Ikari N, Serizawa A, Mitani S, Yamamoto M, Furukawa T
    • Journal Title

      Am J Pathol.

      Volume: 189 Pages: 784-796

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure and function analysis of the C. elegans aminophospholipid translocase TAT-1.2019

    • Author(s)
      Chen YZ, Kloditz K, Lee ES, Nguyen DP, Yuan Q, Johnson J, Lee-Yow Y, Hall A,Mitani S, Xia NS, Fadeel B, Xue D
    • Journal Title

      J Cell Sci.

      Volume: 132

    • DOI

      10.1242/jcs.227660

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase is indispensable for oogenesis, oocyte-to-embryo transition, and larval development of the nematode Caenorhabditis elegans2018

    • Author(s)
      Kanaki Nanako、Matsuda Ayako、Dejima Katsufumi、Murata Daisuke、Nomura Kazuko H、Ohkura Takashi、Gengyo-Ando Keiko、Yoshina Sawako、Mitani Shohei、Nomura Kazuya
    • Journal Title

      Glycobiology

      Volume: 29 Issue: 2 Pages: 163-178

    • DOI

      10.1093/glycob/cwy104

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Imbalanced Expression of Tau and Tubulin Induces Neuronal Dysfunction in C. elegans Models of Tauopathy.2018

    • Author(s)
      Miyasaka T, Shinzaki Y, Yoshimura S, Yoshina S, Kage-Nakadai E, Mitani S, Ihara Y.
    • Journal Title

      Front Neurosci.

      Volume: 12 Pages: 415-415

    • DOI

      10.3389/fnins.2018.00415

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] OFF-responses of interneurons optimize avoidance behaviors depending on stimulus strength via electrical synapses.2018

    • Author(s)
      Hori S, Oda S, Suehiro Y, Iino Y, Mitani S
    • Journal Title

      PLoS Genet.

      Volume: 14 Issue: 6 Pages: e1007477-e1007477

    • DOI

      10.1371/journal.pgen.1007477

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The small GTPase ARF-1.2 is a regulator of unicellular tube formation in Caenorhabditis elegans2018

    • Author(s)
      Kage-Nakadai E, Sun S, Iwata S, Yoshina ,S Nishikawa Y and Mitani S
    • Journal Title

      Journal of Physiological Sciences

      Volume: in press Issue: 1 Pages: 47-56

    • DOI

      10.1007/s12576-018-0617-5

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Somatic mutations and increased lymphangiogenesis observed in a rare case of intramucosal gastric carcinoma with lymph node metastasis2018

    • Author(s)
      Ikari N, Aoyama S, Seshimo A, Suehiro Y, Motohashi T, Mitani S, Yoshina S, Tanji E, Serizawa A, Yamada T, Taniguchi K, Yamamoto M, Furukawa T
    • Journal Title

      Oncotarget

      Volume: 22 Issue: 12 Pages: 10808-10817

    • DOI

      10.18632/oncotarget.24289

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Aneuploidy-Free and Structurally Defined Balancer Chromosome Toolkit for Caenorhabditis elegans2018

    • Author(s)
      Dejima Katsufumi、Hori Sayaka、Iwata Satoru、Suehiro Yuji、Yoshina Sawako、Motohashi Tomoko、Mitani Shohei
    • Journal Title

      Cell Reports

      Volume: 22 Issue: 1 Pages: 232-241

    • DOI

      10.1016/j.celrep.2017.12.024

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive functional genomics using <i>Caenorhabditis elegans</i> as a model organism2017

    • Author(s)
      Mitani S
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 93 Issue: 8 Pages: 561-577

    • DOI

      10.2183/pjab.93.036

    • NAID

      130006164475

    • ISSN
      0386-2208, 1349-2896
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cysteine protease cathepsin B mediates radiation-induced bystander effects.2017

    • Author(s)
      Peng Y, Zhang M, Zheng L, Liang Q, Li H, Chen JT, Guo H, Yoshina S, Chen YZ, Zhao X, Wu X, Liu B, Mitani S, Yu JS, Xue D.
    • Journal Title

      Nature

      Volume: 547 Issue: 7664 Pages: 458-462

    • DOI

      10.1038/nature23284

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic Development2017

    • Author(s)
      Weaver BP, Weaver YM, Mitani S, Han M
    • Journal Title

      Dev Cell

      Volume: 41 Issue: 6 Pages: 665-673

    • DOI

      10.1016/j.devcel.2017.05.013

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] GOP-1 promotes apoptotic cell degradation by activating the small GTPase Rab2 in C. elegans.2017

    • Author(s)
      Yin J, Huang Y, Guo P, Hu S, Yoshina S, Xuan N, Gan Q, Mitani S, Yang C, Wang X.
    • Journal Title

      J Cell Biol.

      Volume: 216 Issue: 6 Pages: 1775-1794

    • DOI

      10.1083/jcb.201610001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel deletion alleles of a C. elegans gene C38D4.9, named as tm4476 and tm45612017

    • Author(s)
      Yoshina S; Hori, S; Suehiro, Y; Mitani, S
    • Journal Title

      Micropublication: biology

      Volume: 1

    • DOI

      10.17912/W2HH32

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel deletion alleles of a C. elegans gene Y48E1C.1, named as tm5468, tm5625 and tm56262017

    • Author(s)
      Hori, S; Suehiro, Y; Yoshina, S; Mitani S
    • Journal Title

      Micropublication: biology

      Volume: 1

    • DOI

      10.17912/W2CQ14

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel deletion alleles of a C. elegans gene Y73E7A.1, named as tm6429 and tm64752017

    • Author(s)
      Suehiro, Y; Yoshina, S; Hori, S; Mitani, S
    • Journal Title

      Micropublication: biology

      Volume: 1

    • DOI

      10.17912/W2808M

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ラットの坐骨神経と下肢骨格筋を用いた容積導体と神経・骨格筋間の信号伝機構を学ぶ実習2017

    • Author(s)
      末廣勇司、榊建二郎、吉名佐和子、堀沙耶香、出嶋克史、岩田悟、三谷昌平
    • Journal Title

      日本生理学雑誌

      Volume: 79 Pages: 44-48

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] One-step homozygosity in precise gene editing by an improved CRISPR/Cas9 system.2016

    • Author(s)
      Zhao P, Zhang Z, Lv X, Zhao X, Suehiro Y, Jiang Y, Wang X, Mitani S, Gong H, Xue D
    • Journal Title

      Cell Res

      Volume: 26 Issue: 5 Pages: 633-636

    • DOI

      10.1038/cr.2016.46

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Impaired NFKBIE gene function decreases cellular uptake of methotrexate by down-regulating SLC19A1 expression in a human rheumatoid arthritis cell line2016

    • Author(s)
      Imamura H, YoshinaS, Ikari K, Miyazawa K, Momohara S, Mitani S
    • Journal Title

      Mod Rheumatol

      Volume: - Issue: 4 Pages: 1-10

    • DOI

      10.3109/14397595.2015.1112481

    • NAID

      120007144512

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endomembrane-associated RSD-3 is important for RNAi induced by extracellular silencing RNA in both somatic and germ cells of Caenorhabditis elegans2016

    • Author(s)
      Imae R, Dejima K, Kage-Nakadai E, Arai H, Mitani S.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 28198-28198

    • DOI

      10.1038/srep28198

    • URL

      https://localhost/en/publications/8510018e-fab8-40df-93d1-302e7c0d5ff5

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oxidative Stress Impairs Cell Death by Repressing the Nuclease Activity of Mitochondrial Endonuclease G2016

    • Author(s)
      Lin JL, Nakagawa A, Skeen-Gaar R, Yang WZ, Zhao P, Zhang Z, Ge X, Mitani S, Xue D, Yuan HS.
    • Journal Title

      Cell Rep

      Volume: 16 Issue: 2 Pages: 279-287

    • DOI

      10.1016/j.celrep.2016.05.090

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mitochondrial endonuclease G mediates breakdown of paternal mitochondria upon fertilization2016

    • Author(s)
      Zhou Q, Li H, Li H, Nakagawa A, Lin JL, Lee ES, Harry BL, Skeen-Gaar RR, Suehiro Y, William D, Mitani S, Yuan HS, Kang BH, Xue D
    • Journal Title

      Science

      Volume: 353 Issue: 6297 Pages: 394-399

    • DOI

      10.1126/science.aaf4777

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The DEG/ENaC cation channel protein UNC-8 drives activity-dependent synapse removal in remodeling GABAergic neurons2016

    • Author(s)
      Miller-Fleming TW, Petersen SC, Manning L, Matthewman C, Gornet M, Beers A, Hori S, Mitani S, Bianchi L, Richmond J, Miller DM
    • Journal Title

      Elife

      Volume: 5

    • DOI

      10.7554/elife.14599

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Caenorhabditis elegans homolog of Prox1/Prospero is expressed in the glia and is required for sensory behavior and cold tolerance.2016

    • Author(s)
      Kage-Nakadai E., Ohta, A., Ujisawa T., Sun S., Nishikawa Y., Kuhara A., Mitani S.
    • Journal Title

      Genes to Cells

      Volume: 21(9) Issue: 9 Pages: 936-948

    • DOI

      10.1111/gtc.12394

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Inhibition of the integrin signal constitutes a mouse iPS cell niche2016

    • Author(s)
      Higuchi S, Yoshina S, Mitani S
    • Journal Title

      Dev Growth Differ

      Volume: 58 Issue: 7 Pages: 586-599

    • DOI

      10.1111/dgd.12302

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Engineering new balancer chromosomes in C. elegans via CRISPR/Cas92016

    • Author(s)
      Iwata S, Yoshina S, Suehiro Y, Hori S, Mitani S
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1

    • DOI

      10.1038/srep33840

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distinct roles of the two VPS33 proteins in the endolysosomal system in Caenorhabditis elegans2016

    • Author(s)
      Gengyo-Ando K, Kage-Nakadai E, Yoshina S, Otori M, Kagawa-Nagamura Y, Nakai J, Mitani S
    • Journal Title

      Traffic

      Volume: 17 Issue: 11 Pages: 1197-1213

    • DOI

      10.1111/tra.12430

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chondroitin 4-O-Sulfotransferase Is Indispensable for Sulfation of Chondroitin and Plays an Important Role in Maintaining Normal Life Span and Oxidative Stress Responses in Nematodes2016

    • Author(s)
      Izumikawa T, Dejima K, Watamoto Y, Nomura KH, Kanaki N, Rikitake M, Tou M, Murata D, Yanagita E, Kano A, Mitani S, Nomura K, Kitagawa H
    • Journal Title

      J Biol Chem.

      Volume: 291 Pages: 23294-23304

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] An endosome-resident zinc transporter is involved in negative regulation of systemic dsRNA spreading in C. elegans2019

    • Author(s)
      Katsufumi Dejima, Rieko Imae, Yuji Suehiro, Shohei Mitani
    • Organizer
      22nd International C. elegans Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cre/LoxP-mediated conditional knockout in C. elegans: toolkit and limits2017

    • Author(s)
      Shohei Mitani
    • Organizer
      21st International C. elegans Conference, UCLA
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 東京女子医科大学医学部生理学(分子細胞生理学分野)

    • URL

      http://www.twmu.ac.jp/physiol2/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] ナショナルバイオリソースプロジェクト「実験動物 線虫」

    • URL

      https://shigen.nig.ac.jp/c.elegans/?lang=japanese

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Remarks] 三谷 昌平 業績DB

    • URL

      https://gyoseki.twmu.ac.jp/twmhp/KgApp?kyoinId=ymkbygoeggy

    • Related Report
      2019 Annual Research Report
  • [Remarks] 東京女子医科大学医学部 生理学講座(分子細胞生理学分野)

    • URL

      http://www.twmu.ac.jp/Basic/physiol2/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 三谷 昌平 業績DB

    • URL

      http://gyoseki.twmu.ac.jp/twmhp/KgApp?kyoinId=ymkbygoeggy

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京女子医科大学医学部第二生理学教室

    • URL

      http://www.twmu.ac.jp/Basic/physiol2/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京女子医科大学教員業績第二生理学

    • URL

      http://gyoseki.twmu.ac.jp/twmhp/KgApp?kozac=C10400000000&year=2016

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] ミトコンドリア保護剤、ミトコンドリア障害改善剤、またはミトコンドリア機能改善剤2020

    • Inventor(s)
      三谷昌平 他
    • Industrial Property Rights Holder
      東京女子医科大学 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 老化防止剤または寿命延長剤2019

    • Inventor(s)
      三谷昌平 他
    • Industrial Property Rights Holder
      東京女子医科大学 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 老化防止剤または寿命延長剤2019

    • Inventor(s)
      三谷昌平 他
    • Industrial Property Rights Holder
      東京女子医科大学 他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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