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Elucidation of the role of TDP-43 in microRNA biogenesis and ALS pathogenesis

Research Project

Project/Area Number 22390176
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionOsaka University

Principal Investigator

KAWAHARA Yukio  大阪大学, 大学院・医学系研究科, 特任准教授 (常勤) (80542563)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2011: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2010: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords神経分子病態学 / ALS / RNA / 神経変性疾患 / 脳神経疾患 / 筋萎縮性側索硬化症 / 痴呆 / 遺伝子
Research Abstract

TDP-43 is a RNA binding protein and associated with the pathogenesis of ALS. However, the physiological functions of TDP-43, especially related to the disease pathogenesis are not fully understood. In this study, we show that TDP-43 facilitates the production of a subset of pre-miRNAs by both interacting with the Drosha complex and binding directly to the relevant pri-miRNAs. Furthermore, cytoplasmic TDP-43, which interacts with the Dicer complex, promotes the processing of some of these pre-miRNAs. Finally, we show that involvement of TDP-43 in miRNA biogenesis is indispensable for neuronal outgrowth. These results support a previously uncharacterized role for TDP-43 in post-transcriptional regulation of miRNA expression.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (27 results)

All 2013 2012 2011 2010 Other

All Journal Article (15 results) (of which Peer Reviewed: 9 results) Presentation (7 results) (of which Invited: 2 results) Book (1 results) Remarks (4 results)

  • [Journal Article] microRNAの機能とその修飾2013

    • Author(s)
      余越萌, 河原行郎
    • Journal Title

      実験医学(増刊)

      Volume: 31(7) Pages: 160-167

    • Related Report
      2012 Final Research Report
  • [Journal Article] Quantification of A-to-I editing of microRNAs using a conventional method2012

    • Author(s)
      Kawahara Y
    • Journal Title

      Nature Protocols

      Volume: 7(7) Pages: 1426-1437

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tissue- and plasma-specific microRNA signatures for atherosclerotic abdominal aortic aneurysm.2012

    • Author(s)
      Kin K, Miyagawa S, Fukushima S, Shirakawa Y, Torikai K, Shimamura K, Kawahara Y, Daimon T, Kuratani T, Sawa Y
    • Journal Title

      Journal of the American Heart Association

      Volume: 1

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Subset of Circulating MicroRNAs are Predictive for Cardiac Death After Discharge for Acute Myocardial Infarction2012

    • Author(s)
      Matsumoto S, Sakata Y, Nakatani D, Suna S, Mizuno H, Shimizu M, Usami M, Sasaki T, Sato H, Kawahara Y, Hamasaki T, Nanto S, Hori M and Komuro I
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 427(2) Pages: 280-284

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] microRNA2012

    • Author(s)
      河原行郎
    • Journal Title

      分子脳血管病

      Volume: 11(4) Pages: 431-434

    • Related Report
      2012 Final Research Report
  • [Journal Article] TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes2012

    • Author(s)
      Kawahara Y and Mieda-Sato I
    • Journal Title

      Proceedings of the National Academy of Sciences U.S.A.

      Volume: 109(9) Pages: 3347-3352

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A subset of circulating microRNAs are predictive for cardiac death after discharge for acute myocardial infarction.2012

    • Author(s)
      Sen Matsumoto
    • Journal Title

      Biochemical and Biophysical Research Communications.

      Volume: 727 Issue: 2 Pages: 280-284

    • DOI

      10.1016/j.bbrc.2012.09.039

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tissue- and plasma-specific microRNA signatures for atherosclerotic abdominal aortic aneurysm.2012

    • Author(s)
      Keiwa Kin
    • Journal Title

      Journal of the American Heart Association

      Volume: e00745 Issue: 5

    • DOI

      10.1161/jaha.112.000745

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantification of A-to-I editing of microRNAs using a conventional method.2012

    • Author(s)
      Yukio Kawahara
    • Journal Title

      Nature Protocols

      Volume: 7 Issue: 7 Pages: 1426-1437

    • DOI

      10.1038/nprot.2012.073

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes2012

    • Author(s)
      河原行郎、佐藤愛
    • Journal Title

      米国科学アカデミー紀要

      Volume: 109(9) Pages: 3347-3352

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] マイクロRNA2011

    • Author(s)
      河原行郎
    • Journal Title

      分子精神医学

      Volume: 11(3) Pages: 172-177

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Journal Article] RNA編集の異常と関連する疾患2010

    • Author(s)
      河原行郎
    • Journal Title

      実験医学(増刊)

      Volume: 28 Pages: 1628-1635

    • Related Report
      2012 Final Research Report
  • [Journal Article] microRNA発現の転写後調節機構2010

    • Author(s)
      河原行郎
    • Journal Title

      生体の科学

      Volume: 61(4) Pages: 308-314

    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Journal Article] RNA編集の異常と関連する疾患2010

    • Author(s)
      河原行郎
    • Journal Title

      実験医学

      Volume: 28巻 Pages: 1628-1635

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Functional relevance of serotonin 2C receptor mRNA editing in anti-depressant- and anxiety-like behabiors.2010

    • Author(s)
      セドリック モンブリュー、河原行郎
    • Journal Title

      Neuropharmacology

      Volume: 59巻 Pages: 468-473

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Small RNAs2013

    • Author(s)
      Kawahara Y
    • Organizer
      The 7th Japanese-French Frontiers of Science Symposium
    • Place of Presentation
      Shiga, Japan
    • Related Report
      2012 Final Research Report
  • [Presentation] ALS関連蛋白質TDP-43は転写後のマイクロRNA生成を促進する2012

    • Author(s)
      河原行郎, 佐藤愛
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2012-05-23
    • Related Report
      2012 Final Research Report
  • [Presentation] TDP-43 promotes neurite outgrowth through the regulation of microRNA biogenesis2012

    • Author(s)
      Kawahara Y
    • Organizer
      The 35th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      Nagoya, Japan
    • Related Report
      2012 Final Research Report
  • [Presentation] Implication of microRNA dysfunction in the pathogenesis of ALS.2010

    • Author(s)
      河原行郎
    • Organizer
      第51回日本神経学会総会
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2010-05-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] ALS関連蛋白質TDP-43は転写後のマイクロRNA生成を促進する

    • Author(s)
      河原 行郎
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京国際フォーラム (東京)
    • Related Report
      2012 Annual Research Report
  • [Presentation] TDP-43 promotes neurite outgrowth through the regulation of microRNA biogenesis

    • Author(s)
      KAWAHARA Yukio
    • Organizer
      第35回日本神経科学学会大会
    • Place of Presentation
      名古屋国際会議場 (愛知)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] small RNAs

    • Author(s)
      KAWAHARA Yukio
    • Organizer
      第7回日仏先端シンポジウム
    • Place of Presentation
      ロイヤルオークホテル (滋賀)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Book] Post-transcriptional gene regulation2011

    • Author(s)
      ルイスバレンチ、河原行郎
    • Publisher
      Wiley-VCH book社(印刷中)
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.osaka-u.ac.jp/pub/rna/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 大阪大学大学院医学系研究科遺伝子機能制御学 業績

    • URL

      http://www.med.osaka-u.ac.jp/pub/rna/publications.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://apprentice.jpn.org/hp/research-kawahara.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://apprentice.jpn.org/hp/research-kawahara.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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