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Regulation of the expression of genome information by RNA-binding proteins

Research Project

Project/Area Number 14035243
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokushima

Principal Investigator

SIOMI Haruhiko  The University of Tokushima, Institute for Genome Research, Professor (60202107)

Co-Investigator(Kenkyū-buntansha) OKANO Hideyuki  Keio University School of Medicine, 医学部, Professor (60160694)
C.SIOMI Mikiko  Institute for Genome Research University of Tokushima, ゲノム機能研究センター, Associate Professor (20322745)
Project Period (FY) 2002 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥123,400,000 (Direct Cost: ¥123,400,000)
Fiscal Year 2006: ¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 2005: ¥24,000,000 (Direct Cost: ¥24,000,000)
Fiscal Year 2004: ¥25,100,000 (Direct Cost: ¥25,100,000)
Fiscal Year 2003: ¥25,100,000 (Direct Cost: ¥25,100,000)
Fiscal Year 2002: ¥25,200,000 (Direct Cost: ¥25,200,000)
KeywordsRNA-binding proteins / RNAi / fragile X syndrome / neuronal stem cells / FMR1 / Musashi / 脆弱X症候群 / 翻訳調節 / RNA結合タンパク質 / AGO2 / siRNA / 翻訳抑制 / ショウジョウバエ / 神経機能 / 神経幹細胞 / 遺伝子発現制御 / miRNA / 神経系前駆細胞 / musashi / 概日リズム / Notch-シグナル
Research Abstract

Work in the project was directed at understanding molecular mechanisms of how gene expression was regulated by RNA-binding proteins at posttranscriptional levels and how the lack of (or mutations in) specific RNA-binding proteins lead to human disease.
As model proteins, we mainly studied two RNA-binding proteins, FMRP and Musashi. FMRP is the product of the fragile X gene, mutations in which cause fragile X syndrome, the most common cause of hereditary mental retardation. We found that a Drosophila homolog of FMRP (dFMR1) forms a complex with AGO2, an essential component of RNAi in Drosophila. The association of dFMR1 with components of RNAi has the implication that defects in an RNAi-related process may cause human disease.
Recent findings demonstrate that translational regulation contributes to cell-fate specification. We found that the evolutionarily conserved, neural RNA-binding protein Musashi, controls neural cell fate. Further we showed that the protein functions in maintenance of the stem-cell state, differentiation, and tumorigenesis by repressing translation of particular mRNAs. We also found that in mammals it might play an important role in activating Notch signalling by repressing translation of the Notch inhibitor m-Numb.

Report

(6 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (70 results)

All 2007 2006 2005 2004 2002 Other

All Journal Article (38 results) (of which Peer Reviewed: 3 results) Presentation (3 results) Book (13 results) Patent(Industrial Property Rights) (5 results) Publications (11 results)

  • [Journal Article] A Slicer-mediated mechanism for rasiRNA 5' end formation in Drosophila.2007

    • Author(s)
      Gunawardane, LS., Saito, K., Nishida, KM., Miyoshi, K., Kawamura, Y., Nagami, T., Siomi, H., Siomi, MC.
    • Journal Title

      Science 315

      Pages: 1587-1590

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expanding RNA physiology : microRNAs in a unicellular organism2007

    • Author(s)
      Haruhiko Siomi et al.
    • Journal Title

      Genes and Development (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A Slicer-mediated mechanism for repeat-associated siRNA 5' end formation in Drosophila2007

    • Author(s)
      Gunawardane L.S. et al.
    • Journal Title

      Science 315

      Pages: 1587-1590

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Musashi-1 expression in postnatal mouse olfactory epithelium.2007

    • Author(s)
      Watanabe K et al.
    • Journal Title

      Neuroreport. 18

      Pages: 641-644

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Impaired motor functions in mice lacking the RNA-binding protein Hzf2007

    • Author(s)
      Iijima T et al.
    • Journal Title

      Neurosci Res (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] In vitro pre-miRNA processing assays using Drosophila S2 cell lysates.2006

    • Author(s)
      Ishizuka, A., Saito, K., Siomi, MC, Siomi, H.
    • Journal Title

      Methods in Molecular Biology series. (ed., Ying, Shao-Yao) Volume # : 342.

      Pages: 277-286

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome2006

    • Author(s)
      Kuniaki Saito et al.
    • Journal Title

      Genes and Development 20

      Pages: 2214-2222

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Wnt signaling and a Hox protein cooperatively regulate psa-3/Meis to determine daughter cell fate after asymmetric cell division in C. elegans.2006

    • Author(s)
      Arata Y et al.
    • Journal Title

      Dev Cell 11

      Pages: 105-115

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury.2006

    • Author(s)
      Okada S et al.
    • Journal Title

      Nat Med 12

      Pages: 829-834

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Musashil antigen expression in human fetal germinal matrix development2006

    • Author(s)
      Chan C et al.
    • Journal Title

      Exp Neurol 201

      Pages: 515-518

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A carbohydrate-binding protein, Galectin-1, promotes proliferation of adult neural stem cells.2006

    • Author(s)
      Sakaguchi M et al.
    • Journal Title

      Proc Nat1 Acad Sci U S A 103

      Pages: 7112-7117

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice.2006

    • Author(s)
      Hara T et al.
    • Journal Title

      Nature 441

      Pages: 885-889

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distinct functions of human numb isoforms revealed by misexpression in the neural stem cell lineage in the Drosophila larval brain.2006

    • Author(s)
      Toriya M
    • Journal Title

      Dev Neurosci 28

      Pages: 142-155

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Alvarez-Buylla A.New neurons follow the flow of cerebrospinal fluid in the adult brain.2006

    • Author(s)
      Sawamoto K
    • Journal Title

      Science 311

      Pages: 629-632

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Expression of RNA-binding protein Musashi in hair follicle development and hair cycle progression.2006

    • Author(s)
      Sugiyama-Nakagiri Y
    • Journal Title

      Am J Pathol 168

      Pages: 80-92

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Expression of Musashi-1 in the rat stomach and changes during mucosal injury and reconstitution.2006

    • Author(s)
      Nagata H
    • Journal Title

      FEBS Lett 580

      Pages: 27-33

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression of RNA-binding protein Musashi in hair follicle development and hair cycle progression.2006

    • Author(s)
      Sugiyama-Nakagiri Y
    • Journal Title

      American J.Pathology 168

      Pages: 80-92

    • Related Report
      2005 Annual Research Report
  • [Journal Article] New neurons follow the flow of cerebrospinal fluid in the adult brain.2006

    • Author(s)
      Sawamoto, K
    • Journal Title

      Science 311

      Pages: 629-631

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A carbohydrate binding protein, Galectin- 1, promotes proliferation of adult neural stem cells.2006

    • Author(s)
      Sakaguchi M
    • Journal Title

      Proc.Natl.Acad.Sci.USA (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Suppression of autophagy in neural cells causes a neurodegenerative disease2006

    • Author(s)
      Hara T
    • Journal Title

      Nature (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Slicer function of Drosophila Argonautes and its involvement in RISC formation.2005

    • Author(s)
      Keita Miyoshi et al.
    • Journal Title

      Genes & Development 19

      Pages: 2837-2848

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A potential link between transgene silencing and poly(A) tails2005

    • Author(s)
      Mikiko C.Siomi et al.
    • Journal Title

      RNA2005 11

      Pages: 1004-1011

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells.2005

    • Author(s)
      Kuniaki Saito et al.
    • Journal Title

      Plos Biology 3・7

    • Related Report
      2005 Annual Research Report
  • [Journal Article] dentification of components of RNAi pathways using the Tandem Affinity Purification (TAP) method.2005

    • Author(s)
      Mikiko C.Siomi et al.
    • Journal Title

      Methods in Molecular Biology 2005 309

      Pages: 1-9

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Involvement of Hu and hnRNP K in neuronal differentiation through p21 mRNA post-transcriptional regulation.2005

    • Author(s)
      Yano M
    • Journal Title

      J.Biol.Chem. 280

      Pages: 12690-12699

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine.2005

    • Author(s)
      Matsumoto T
    • Journal Title

      Gasteroenterology 128

      Pages: 1851-1867

    • Related Report
      2005 Annual Research Report
  • [Journal Article] RNA-binding protein HZf specifically binds to 3'-untranslated region of type 1 inositol 1,4,5-trisphosphate receptor mRNA and is involved in its dendritic localization.2005

    • Author(s)
      Iijima T
    • Journal Title

      Proc.Natl.Acad.Sci.USA 102

      Pages: 17190-17195

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Function of RNA binding protein Musashi-1 in stem cells.Exp.2005

    • Author(s)
      Okano H
    • Journal Title

      Cell Res 306

      Pages: 349-356

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identification of components of RNAi pathways using the Tandem Affinity Purification (TAP) method.2005

    • Author(s)
      Siomi, MC., Siomi, H
    • Journal Title

      Methods in Mol.Biol (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Processing of Pre-microRNAs by the Dicer-1-Loquacious Complex in Drosophila Cells2005

    • Author(s)
      Saito, K., Ishizuka, A., Siomi, H., Siomi, MC.
    • Journal Title

      PLoS Biology (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The RNA-binding protein HuD regulates neuronal cell identity and maturation.2005

    • Author(s)
      Akamatsu W, 10人, Okano H.
    • Journal Title

      Proc Natl Acad Sci USA. 102

      Pages: 4625-4630

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of Hu and Heterogeneous Nuclear Ribonucleoprotein K in Neuronal Differentiation through p21 mRNA Post-transcriptional Regulation.2005

    • Author(s)
      Yano M, Okano HJ, Okano H
    • Journal Title

      J Biol Chem. 280

      Pages: 12690-12699

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways2004

    • Author(s)
      Okamura, K., Ishizuka, A., Siomi, H., Siomi, MC.
    • Journal Title

      Genes & Development 18

      Pages: 1655-1666

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways.2004

    • Author(s)
      Okamura, K., Ishizuka, A., Siomi, H., Siomi, MC.
    • Journal Title

      Genes & Development 18

      Pages: 1655-1666

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] RNA Interference : A New Mechanism by Which FMRP Acts in the Normal Brain? - What can Drosophila teach us? -2004

    • Author(s)
      Siomi, H., Ishizuka, A, Siomi, MC
    • Journal Title

      MRDDR review 10

      Pages: 68-74

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins2002

    • Author(s)
      Ishizuka, A., Siomi, MC., Siomi, H.
    • Journal Title

      Genes & Development 16

      Pages: 2497-2508

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins.2002

    • Author(s)
      Ishizuka, A., Siomi, MC., Siomi, H.
    • Journal Title

      Genes & Development 16

      Pages: 2497-2508

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vitro precursor micro RNA processing assays using Drosophila Schneider-2 cell lysate.

    • Author(s)
      Akira Ishizuka et al.
    • Journal Title

      Methods in Molecular Biology (In press)

    • Related Report
      2005 Annual Research Report
  • [Presentation] A link between RNAi and human disease2006

    • Author(s)
      塩見 春彦
    • Organizer
      CDB Symposium 2006 -Logic of Development : New Strategies and Concepts
    • Place of Presentation
      神戸
    • Year and Date
      2006-04-23
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Presentation] A link between RNAi and fragile X syndrome.2006

    • Author(s)
      H. Siomi
    • Organizer
      Japan-Taiwan Conference on Cellular and Molecular Neurobiology
    • Place of Presentation
      RIKEN Brain Science Institute, Wako, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Presentation] A link between RNAi and disease.2006

    • Author(s)
      H. Siomi
    • Organizer
      CDB Symposium 2006 -Logic of Development : New Strategies and Concepts
    • Place of Presentation
      Kobe, Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Methods in Molecular Biology2006

    • Author(s)
      Ishizuka, A., Saito, K., Siomi, MC., Siomi, H
    • Total Pages
      359
    • Publisher
      Humana
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Methods in Molecular Biology2006

    • Author(s)
      Akira Ishizuka et al.
    • Total Pages
      10
    • Publisher
      Humana Press
    • Related Report
      2006 Annual Research Report
  • [Book] Neural stem cells : Isolation and self-renewal. In Tissue Stem Cells ; Biology & Applications.2006

    • Author(s)
      Okano H
    • Total Pages
      16
    • Publisher
      Taylor & Francis Group, LLC, New York
    • Related Report
      2005 Annual Research Report
  • [Book] Transplantation of neural stem cells for spinal cord regeneration. In Encyclopedic References of Neuroscience2006

    • Author(s)
      Okano H
    • Publisher
      Springer-Verlag(In press)
    • Related Report
      2005 Annual Research Report
  • [Book] RNA工学の最前線2005

    • Author(s)
      三好啓太ら
    • Total Pages
      11
    • Publisher
      シーエムシー出版
    • Related Report
      2005 Annual Research Report
  • [Book] 化学と生物2005

    • Author(s)
      春原隆史ら
    • Total Pages
      7
    • Publisher
      学会出版センター
    • Related Report
      2005 Annual Research Report
  • [Book] Bio Clinica2005

    • Author(s)
      齋藤都暁ら
    • Total Pages
      6
    • Publisher
      北隆館
    • Related Report
      2005 Annual Research Report
  • [Book] Bio Clinica2005

    • Author(s)
      三好啓太ら
    • Total Pages
      7
    • Publisher
      北隆館
    • Related Report
      2005 Annual Research Report
  • [Book] 実験医学2005

    • Author(s)
      齋藤都暁ら
    • Total Pages
      1
    • Publisher
      羊土社
    • Related Report
      2005 Annual Research Report
  • [Book] RNAi法とアンチセンス法2005

    • Author(s)
      石塚明ら
    • Total Pages
      12
    • Publisher
      講談社
    • Related Report
      2005 Annual Research Report
  • [Book] RNAi法とアンチセンス法2005

    • Author(s)
      三好啓太ら
    • Total Pages
      10
    • Publisher
      講談社
    • Related Report
      2005 Annual Research Report
  • [Book] Pediatric Nutrition in Chronic Diseases and Developmental Disorders - Prevention, Assessment, and Treatment- 2nd Edition.2005

    • Author(s)
      Nelson D.et al.
    • Total Pages
      3
    • Publisher
      Oxford university Press, New York.
    • Related Report
      2005 Annual Research Report
  • [Book] The molecular mechanisms of mRNA export. pp161-174. In Nuclear Import and Export in Plants and Animals. (ed., Tzfira, T Citovsky, V.)2004

    • Author(s)
      Taura, T., Siomi, M.C., Siomi, H
    • Publisher
      Landes Bioscience, New York.
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 神経幹細胞の増殖抑制剤2006

    • Inventor(s)
      岡野栄之
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Industrial Property Number
      2006-034444
    • Filing Date
      2006-02-10
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] 平滑筋幹細胞2006

    • Inventor(s)
      丸山哲夫
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Industrial Property Number
      2006-022875
    • Filing Date
      2006-01-31
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] 脊髄損傷治療剤2005

    • Inventor(s)
      岡野栄之
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Industrial Property Number
      2005-270915
    • Filing Date
      2005-09-16
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] ヒトグリオーマ治療に有用なリコンビナントHSV2005

    • Inventor(s)
      矢崎貴仁
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Industrial Property Number
      2005-315414
    • Filing Date
      2005-10-28
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] 動物モデルとその作製方法2005

    • Inventor(s)
      丸山哲夫
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Industrial Property Number
      2005-332113
    • Filing Date
      2005-11-16
    • Related Report
      2005 Annual Research Report
  • [Publications] Siomi, H., Ishizuka, A, Siomi, MC: "RNA Interference : A New Mechanism by Which FMRP Acts in the Normal Brain? -What can Drosophila teach us?"MRDDR review. 10. 68-74 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyanoiri Y, Kobayashi H, Imai T, Watanabe M, Nagata T, Uesugi S, Okano H, Katahira M.: "Origin of higher affinity to RNA of the N-terminal RNA-binding domain than that of the C-terminal one of a mouse neural protein, musashi1, as revealed by comparison of their structures, modes of interaction, surface electrostatic potentials, and backbone dynamics"J Biol Chem. 278. 41309-41315 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishizuya-Oka A, Shimizu K, Sakakibara S, Okano H, Ueda S.: "Thyroid hormone-upregulated expression of Musashi-1 is specific for progenitor cells of the adult epithelium during amphibian gastrointestinal remodeling."J Cell Sci.. 116. 3157-3164 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Taura, T., Siomi, M.C., Siomi, H.: "Nuclear transport of RNA and proteins (The molecular mechanisms of mRNA export)(ed., Citovsky, V. and Tzfira, T.)"Landes Bioscience, New York(未定). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tabara, H., et al.: "The double-stranded RNA binding protein RDE-4 interacts in vivo with RDE-1, DCR-1 and a conserved DExH-box helicase to direct RNA interference in C.elegans"Cell. 109. 861-871 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Inoue, SB., et al.: "A role for the fragile X mental retardation gene in the Drosophila circadian rhythms"Current Biology. 12. 1331-1335 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishizuka, A., et al.: "A Drosophila fragile X protein interacts with components of RNAi and ribosomal Proteins"Genes & Development. 16. 2497-2508 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Siomi, MC., et al.: "Casein kinase II phosphorylates the fragile X syndrome protein and modulates its biological properties"Mol Cell Biol. 22. 8438-8447 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakakibara S., et al.: "RNA-Binding Protein Musashi Family, Roles for CNS Stem Cells and a Subpopulation of Ependymal Cells Revealed by Targeted Disruption and Antisense Ablation"Proc Natl Acad Sci USA. 99. 15194-15199 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuno K., et al.: "Involvement of a proline-rich motif and RING-H2 finger of Deltex in the regulation of Notch signaling"Development. 129. 1049-1059 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Taura, T., et al.: "The molecular mechanisms of mRNA export. In Nuclear transport RNA and proteins.(ed., Citovsky, V.and Tzfira, T.)"Landes Bioscience, New York (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2018-03-28  

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