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Functional role of hTERT-RMRP complex in stem cells and tumor initiating cells

Research Project

Project/Area Number 21689012
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionNational Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East

Principal Investigator

MASUTOMI Kenkichi  独立行政法人国立がん研究センター, 研究所, 分野長 (20450570)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥28,080,000 (Direct Cost: ¥21,600,000、Indirect Cost: ¥6,480,000)
Fiscal Year 2010: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2009: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Keywords癌 / 幹細胞 / 生化学
Research Abstract

Constitutive expression of telomerase in human cells prevents the onset of senescence and crisis by maintaining telomere homeostasis. However, accumulating evidence suggests that the human telomerase catalytic subunit (hTERT) contributes to cell physiology independent of its ability to elongate telomeres. Here we show that hTERT interacts with the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), a gene that is mutated in the inherited pleiotropic syndrome Cartilage-Hair Hypoplasia. hTERT and RMRP form a distinct ribonucleoprotein complex that exhibits RNA dependent RNA polymerase (RdRP) activity and produces double-stranded RNAs that can be processed into small interfering RNA in a Dicer-dependent manner. These observations identify a mammalian RdRP composed of hTERT in complex with RMRP (Nature 2009, Maida et al.).

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (60 results)

All 2011 2010 2009 2008 Other

All Journal Article (18 results) (of which Peer Reviewed: 6 results) Presentation (35 results) Book (2 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Two-step cleavage of hairpin RNA with 5' overhangs by human DICER2011

    • Author(s)
      Ando Y, Maida Y, Morinaga A, Burroughs AM, Kimura R, Chiba J, Suzuki H, Masutomi K, Hayashizaki Y.
    • Journal Title

      BMC Molecular Biology 12

      Pages: 6-6

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] RNA-dependent RNA polymerase in RNA silencing2011

    • Author(s)
      Maida Y, Masutomi K.
    • Journal Title

      Biological Chemistry 392

      Pages: 299-304

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Two-step cleavage of hairpin RNA with 5' overhangs by human DICER2011

    • Author(s)
      Ando Y, Masutomi K, et al
    • Journal Title

      BMC Molecular Biology

      Volume: Feb 9;12 Pages: 6-6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RNA-dependent RNA polymerase in RNA silencing2011

    • Author(s)
      Maida Y, Masutomi K
    • Journal Title

      Biological Chemistry

      Volume: 392 Pages: 299-304

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] テロメレース:テロメア伸長反応と新たな機能2010

    • Author(s)
      木下圭太、毎田佳子、増富健吉
    • Journal Title

      科学と生物 48(11)

      Pages: 780-784

    • NAID

      10027728825

    • Related Report
      2010 Final Research Report
  • [Journal Article] TERT,がん性幹細胞を標的としたがん治療の可能性2010

    • Author(s)
      岡本奈緒子, 増富健吉
    • Journal Title

      腫瘍内科 6(1)

      Pages: 59-64

    • NAID

      40017273177

    • Related Report
      2010 Final Research Report
  • [Journal Article] テロメア・テロメレースとnoncoding RNAとの新たな関わり2010

    • Author(s)
      毎田佳子, 増富健吉
    • Journal Title

      実験医学増刊 28(10)

      Pages: 1521-1527

    • Related Report
      2010 Final Research Report
  • [Journal Article] ヒト二本鎖RNA合成酵素の発見とRNAサイレンシングへの関与2010

    • Author(s)
      毎田佳子, 増富健吉
    • Journal Title

      細胞工学 29(4)

      Pages: 374-375

    • Related Report
      2010 Final Research Report
  • [Journal Article] ヒトRNA依存性RNAポリメラーゼの発見とRNAサイレンシングへの関与2010

    • Author(s)
      毎田佳子, 増富健吉
    • Journal Title

      実験医学(カレントトピックス) 28(3)

      Pages: 439-443

    • Related Report
      2010 Final Research Report
  • [Journal Article] テロメレース:テロメア伸長反応と新たな機能2010

    • Author(s)
      木下圭太、毎田佳子、増富健吉
    • Journal Title

      科学と生物

      Volume: 48 Pages: 780-784

    • NAID

      10027728825

    • Related Report
      2010 Annual Research Report
  • [Journal Article] TERT,がん性幹細胞を標的としたがん治療の可能性2010

    • Author(s)
      岡本奈緒子、増富健吉
    • Journal Title

      腫瘍内科

      Volume: 6 Pages: 59-64

    • NAID

      40017273177

    • Related Report
      2010 Annual Research Report
  • [Journal Article] ヒトRNA依存性RNAポリメラーゼの発見とRNAサイレンシングへの関与2010

    • Author(s)
      毎田佳子, 増富健吉
    • Journal Title

      実験医学 28

      Pages: 439-443

    • Related Report
      2009 Annual Research Report
  • [Journal Article] An RNA dependent RNA polymerase formed by TERT and the RMRP RNA2009

    • Author(s)
      Maida Y, Yasukawa M, Furuuchi M, Lassmann T, Possemato R, Okamoto N, Kasim V, Hayashizaki Y, Hahn WC, Masutomi K.
    • Journal Title

      Nature 461

      Pages: 230-235

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] RNA依存性RNAポリメラーゼをめぐる新たな展望2009

    • Author(s)
      毎田佳子, 増富健吉
    • Journal Title

      Medical Science Digest(2009年12月号特集「RNAと医薬品」) 35

      Pages: 571-577

    • Related Report
      2010 Final Research Report
  • [Journal Article] 小分子RNAと疾患2009

    • Author(s)
      毎田佳子, 増富健吉
    • Journal Title

      BIO Clinica 24(8)

    • Related Report
      2010 Final Research Report
  • [Journal Article] An RNA dependent RNA polymerase formed by TERT and the RMRP RNA2009

    • Author(s)
      Maida Y, Masutomi K, et al
    • Journal Title

      Nature 461

      Pages: 230-235

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RNA依存性RNAポリメラーゼをめぐる新たな展望2009

    • Author(s)
      毎田佳子, 増富健吉
    • Journal Title

      Medical Science Digest 35

      Pages: 571-577

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 小分子RNAと疾患2009

    • Author(s)
      毎田佳子, 増富健吉
    • Journal Title

      BIO Clinica 24

      Pages: 718-723

    • Related Report
      2009 Annual Research Report
  • [Presentation] Induction of tumor initiating cell behavior of defined genetic composition by a complex composed of nucleostemin, hTERT and BRG12011

    • Author(s)
      Okamoto N, Yasukawa M, Nguyen C, Possemato R, Fukami K, Hahn WC, Masutomi K.
    • Organizer
      Keystone Symposia "Stem Cells, Cancer and Metastasis"(ポスター発表)
    • Place of Presentation
      Keystone Resort, Keystone, Colorado
    • Related Report
      2010 Final Research Report
  • [Presentation] Induction of tumor initiating cell behavior of defined genetic composition by a complex composed of nucleostemin, hTERT and BRG12011

    • Author(s)
      Okamoto N, Masutomi K, et al
    • Organizer
      Keystone Symposia "Stem Cells, Cancer and Metastasis"
    • Place of Presentation
      Keystone Resort, Keystone, Colorado
    • Related Report
      2010 Annual Research Report
  • [Presentation] テロメレース新規機能とがん幹細胞2010

    • Author(s)
      増富健吉
    • Organizer
      第6回宮崎サイエンスキャンプ
    • Place of Presentation
      ワールドコンベンションセンターサミット宮崎
    • Year and Date
      2010-02-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] A mammalian RNA dependent RNA polymerase formed by hTERT and the RNA component of RNase MRP2010

    • Author(s)
      Masutomi K
    • Organizer
      Joint Colloquium : "Current approaches and future perspectives on the human genome,trancriptome and proteome" Nobel Forum(招待講演)
    • Place of Presentation
      Karolinska Institute, Stockholm
    • Year and Date
      2010-01-19
    • Related Report
      2010 Final Research Report
  • [Presentation] A mammalian RNA dependent RNA polymerase formed by hTERT and the RNA component of RNase MRP2010

    • Author(s)
      Masutomi K
    • Organizer
      Joint Colloquium : "Current approaches and future perspectives on the human genome, trancriptome and proteome" Nobel Forum
    • Place of Presentation
      Karolinska Institute, Stockholm
    • Year and Date
      2010-01-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] がん幹細胞と放射線療法抵抗性2010

    • Author(s)
      増富健吉
    • Organizer
      第69回日本癌学会総会(招待講演)
    • Place of Presentation
      大阪国際会議場、リーガロイヤルホテル大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] hTERT、BRG1、核小体GTP結合タンパク質GNL3L/NSからなる複合体は腫瘍形成能を制御する2010

    • Author(s)
      岡本奈緒子、安川麻美、Christine Nguyen、Kasim Vivi、深見希代子、William C.Hahn、増富健吉
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪国際会議場、リーガロイヤルホテル大阪(口頭発表)
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒトRNA依存性RNAポリメラーゼとクロマチン構造維持2010

    • Author(s)
      増富健吉
    • Organizer
      第2回日本RNAi研究会(招待講演)
    • Place of Presentation
      グランドプリンスホテル広島
    • Related Report
      2010 Final Research Report
  • [Presentation] テロメレース、がん幹細胞、転移2010

    • Author(s)
      増富健吉
    • Organizer
      第19回日本がん転移学会学術集会・総会(招待講演)
    • Place of Presentation
      金沢市文化ホール
    • Related Report
      2010 Final Research Report
  • [Presentation] Human RNA dependent RNA polymerase and chromatin structure2010

    • Author(s)
      増富健吉
    • Organizer
      第62回日本細胞生物学会大会(招待講演)
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2010 Final Research Report
  • [Presentation] Immunohistchemical analysis of CD133/44 expression in surgical specimens of squamous cell carcinoma of the esophagus after neoadjuvant chemotherapy2010

    • Author(s)
      Nakajima Eguchi T, Yoshida H, Taniguchi H, Masutomi K, Shimoda T, Yamada Y.
    • Organizer
      AACR 101^<st> Annual meeting 2010, Walter E.Washington Convention Center(ポスター発表)
    • Place of Presentation
      Whasington, DC
    • Related Report
      2010 Final Research Report
  • [Presentation] Evaluation of CD133/44 expression level in reacted gastric cancer tissues after neoadjuvant chemotherapy2010

    • Author(s)
      Yoshida H, Nakajima Eguchi T, Taniguchi H, Horita Y, Masutomi K, Shimoda T, Yamada Y.
    • Organizer
      AACR 101^<st> Annual meeting 2010, Walter E. Washington Convention Center(ポスター発表)
    • Place of Presentation
      Whasington, DC
    • Related Report
      2010 Final Research Report
  • [Presentation] A complex of hTERT, Brg1 and the nucleolar GTP-binding proteins GNL3L and nucleostemin regulates tumor initiating cell behavior Cold Spring Harbor Asia Conferences "James Watson Symposium on Cancer"2010

    • Author(s)
      Okamoto N, Yasukawa M, Nguyen C, Possemato R, Fukami K, Hahn WC, Masutomi K.
    • Organizer
      Suzhou Dushu Lake Conference Center
    • Place of Presentation
      Suzhou, China(口頭発表)
    • Related Report
      2010 Final Research Report
  • [Presentation] テロメレース新規機能とがん幹細胞2010

    • Author(s)
      増富健吉
    • Organizer
      第6回宮崎サイエンスキャンプワールドコンベンションセンターサミット宮崎(招待講演)
    • Related Report
      2010 Final Research Report
  • [Presentation] Immunohistchemical analysis of CD133/44 expression in surgical specimens of squamous cell carcinoma of the esophagus after neoadjuvant chemotherapy2010

    • Author(s)
      Eguchi T, Masutomi K, et al
    • Organizer
      AACR 101^<st> Annual meeting 2010
    • Place of Presentation
      Washington Convention Center, Whasington, DC
    • Related Report
      2010 Annual Research Report
  • [Presentation] A complex of hTERT, Brg1 and the nucleolar GTP-binding protein GNL3L and nucleostemin regulates tumor initiating cell behavior2010

    • Author(s)
      Okamoto N, Masutomi K, et al
    • Organizer
      Cold Spring Harbor Asia Conferences "James Watson Symposium on Cancer"
    • Place of Presentation
      Suzhou Dushu Lake Conference Center, Suzhou, China
    • Related Report
      2010 Annual Research Report
  • [Presentation] がん幹細胞と放射線療法抵抗性2010

    • Author(s)
      増富健吉
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪国際会議場、リーガロイヤルホテル大阪
    • Related Report
      2010 Annual Research Report
  • [Presentation] hTERT、BRG1、核小体GTP結合タンパク質GNL3L/NSからなる複合体は腫瘍形成能を制御する2010

    • Author(s)
      岡本奈緒子、増富健吉
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪国際会議場、リーガロイヤルホテル大阪
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヒトRNA依存性RNAポリメラーゼとクロマチン構造維持2010

    • Author(s)
      増富健吉
    • Organizer
      第2回日本RNAi研究会
    • Place of Presentation
      グランドプリンスホテル広島
    • Related Report
      2010 Annual Research Report
  • [Presentation] テロメレース、がん幹細胞、転移2010

    • Author(s)
      増富健吉
    • Organizer
      第19回日本がん転移学会学術集会・総会
    • Place of Presentation
      金沢市文化ホール
    • Related Report
      2010 Annual Research Report
  • [Presentation] Human RNA dependent RNA polymerase and chromatin structure2010

    • Author(s)
      増富健吉
    • Organizer
      第62回日本細胞生物学会大会
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2010 Annual Research Report
  • [Presentation] hTERT produces endogenous siRNA through its RNA dependent RNA polymerase activity2009

    • Author(s)
      毎田佳子、増富健吉
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-12-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] hTERTと核小体GTP結合タンパク質NS/GNL3Lによる腫瘍形成能の制御2009

    • Author(s)
      岡本奈緒子、増富健吉
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-12-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] A Mammalian RNA Dependent RNA Polymerase Formed by hTERT and the RNA Component of RNase MRP2009

    • Author(s)
      Masutomi K
    • Organizer
      2010 Keystone Symposia on Molecular and Cellular Biology "Telomere Biology and DNA Repair"
    • Place of Presentation
      RAVC Royal Pine Resort Ashmore, Queensland, Australia
    • Year and Date
      2009-10-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] hTERTはRNA依存性RNAポリメラーゼ活性により内在性siRNAの産生に関与する2009

    • Author(s)
      毎田佳子、増富健吉
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] hTERTと核小体GTP結合タンパク質GNL3L/NSは腫瘍形成能を制御する2009

    • Author(s)
      岡本奈緒子、増富健吉
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] hTERTと核小体GTP結合タンパク質Nucleostemin/GNL3Lによる腫瘍形成能の制御2009

    • Author(s)
      岡本奈緒子、増富健吉
    • Organizer
      第2回SYMPHONY
    • Place of Presentation
      ホテルメトロポリタンエドモンド飯田橋、東京
    • Year and Date
      2009-09-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] A mammalian RNA dependent RNA polymerase (RdRP) formed by hTERT and the RNA component of RNase MRP2009

    • Author(s)
      Masutomi K
    • Organizer
      Cold Sprig Harbor Laboratory Meeting "Telomere and Telomerase"
    • Place of Presentation
      Cold Sprig Harbor, New York
    • Year and Date
      2009-04-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] hTERT produces endogenous siRNA through its RNA dependent RNA polymerase activity2009

    • Author(s)
      毎田佳子、安川麻美、岡本奈緒子、Vivi Kasim、Timo Lassmann、林崎良英、増富健吉
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(口頭発表)
    • Related Report
      2010 Final Research Report
  • [Presentation] hTERTと核小体GTP結合タンパク質NS/GNL3Lによる腫瘍形成能の制御2009

    • Author(s)
      岡本奈緒子、安川麻美、毎田佳子、工富知子、深見希代子、William C.Hahn、増富健吉
    • Organizer
      第32回日本分子生物学会年会(ポスター発表)
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] A Mammalian RNA Dependent RNA Polymerase Formed by hTERT and the RNA Component of RNase MRP2009

    • Author(s)
      Masutomi K
    • Organizer
      2010 Keystone Symposia on Molecular and Cellular Biology "Telomere Biology and DNA Repair" RAVC Royal Pine Resort Ashmore
    • Place of Presentation
      Queensland, Australia(口頭発表)
    • Related Report
      2010 Final Research Report
  • [Presentation] hTERTと核小体GTP結合タンパク質GNL3L/NSは腫瘍形成能を制御する2009

    • Author(s)
      岡本奈緒子、安川麻美、毎田佳子、工富知子、深見希代子、William C.Hahn、増富健吉
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜(口頭発表)
    • Related Report
      2010 Final Research Report
  • [Presentation] hTERTはRNA依存性RNAポリメラーゼ活性により内在性siRNAの産生に関与する2009

    • Author(s)
      毎田佳子、安川麻美、Vivi Kasim、Timo Lassmann、岡本奈緒子、林崎良英、William C.Hahn、増富健吉
    • Organizer
      第68回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜(口頭発表)
    • Related Report
      2010 Final Research Report
  • [Presentation] hTERTと核小体GTP結合タンパク質Nucleostemin/GNL3Lによる腫瘍形成能の制御2009

    • Author(s)
      岡本奈緒子、増富健吉
    • Organizer
      第2回SYMPHONY
    • Place of Presentation
      ホテルメトロポリタンエドモンド飯田橋
    • Related Report
      2010 Final Research Report
  • [Presentation] A mammalian RNA dependent RNA polymerase (RdRP) formed by hTERT and the RNA component of RNase MRP2009

    • Author(s)
      Masutomi K
    • Organizer
      Cold Sprig Harbor Laboratory Meeting "Telomere and Telomerase"
    • Place of Presentation
      (口頭発表)
    • Related Report
      2010 Final Research Report
  • [Book] Capter 8 : Off-telomerase function of telomerase(John Wiley & Sons)

    • Author(s)
      Masutomi K, Hahn WC.
    • Publisher
      Telomerases : Chemistry, Biology and Clinical Applications(in press.)
    • Related Report
      2010 Final Research Report
  • [Book] Telomerases : Chemistry, Biology and Clinical Applications

    • Author(s)
      Masutomi K, Hahn WC.
    • Publisher
      John Wiles & Sons(in press)
    • Related Report
      2010 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.ncc.go.jp/jp/nccri/divisions/p10cell/p10cell.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.ncc.go.jp/jp/nccri/divisions/p10cell/p10cell.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.ncc.go.jp/jp/nccri/divisions/p10cell/p10cell.html

    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] A mammalian RNA dependent RNA Polymerase2009

    • Inventor(s)
      増富健吉, 他
    • Industrial Property Rights Holder
      国立がんセンター, 他
    • Filing Date
      2009-07-06
    • Related Report
      2009 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] A mammalian RNA dependent RNA polymerase2008

    • Inventor(s)
      増富健吉, 他
    • Industrial Property Rights Holder
      国立がん研究センター, 他
    • Filing Date
      2008-08-12
    • Related Report
      2010 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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