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2012 Fiscal Year Final Research Report

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

Research Project

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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
Keywords神経分子病態学 / ALS / RNA / 神経変性疾患
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.

  • Research Products

    (13 results)

All 2013 2012 2011 2010 Other

All Journal Article (9 results) (of which Peer Reviewed: 4 results) Presentation (3 results) Remarks (1 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

  • [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

    • 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 Pages: e000745

    • 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

    • 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

  • [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

    • 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

  • [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

  • [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

  • [Presentation] Small RNAs2013

    • Author(s)
      Kawahara Y
    • Organizer
      The 7th Japanese-French Frontiers of Science Symposium
    • Place of Presentation
      Shiga, Japan
    • Year and Date
      20130125-27
  • [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
    • Year and Date
      20120918-22
  • [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
  • [Remarks]

    • URL

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

URL: 

Published: 2014-08-29  

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