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2012 Fiscal Year Final Research Report

Defective RNA metabolism in motor neurons from Amyotrophic Lateral Scelosis patients

Research Project

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Project/Area Number 23700455
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurochemistry/Neuropharmacology
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

TSUIJI Hitomi  独立行政法人理化学研究所, 運動ニューロン変性研究チーム, 研究員 (40455358)

Project Period (FY) 2011 – 2012
KeywordsALS / spliceosome / snRNP / TDP-43 / RNA
Research Abstract

Neurodegenerative diseases are characterized by the death of specific type of neurons. The motor neuron diseases amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are caused by dysfunction of TDP-43, RNA-binding protein and SMN, essential for biogenesis of spliceosomal component snRNPs, respectively. However, the defects in RNA metabolism common to these diseases remain unclear. We show that TDP-43 localizes in nuclear gems through association with the SMN complex, and is involved in spliceosome maintenance. Moreover, gems are lost, U snRNA levels are up-regulated and spliceosomal U snRNPs abnormally and extensively accumulate in the nuclei of ALS motor neurons but not in the temporal lobe of FTLD with TDP-43 pathology. Together, these findings indicate that collapse of spliceosome stability is the critical process common to neurodegeneration in ALS and SMA, and may explain cell-type specific vulnerability of motor neurons.

  • Research Products

    (12 results)

All 2013 2012 2011

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (11 results)

  • [Journal Article] Spliceosome integrity is defective in motor neuron disease ALS and SMA2013

    • Author(s)
      Tsuiji H., Iguchi Y., Furuya A., Kataoka A., Hatsuta H., Atsuta N., Tanaka F., Hashizume Y., Akatsu H., Murayama S., Sobue G., Yamanaka K
    • Journal Title

      EMBO Molecular Medicine

      Volume: 5(2) Pages: 221-34

    • Peer Reviewed
  • [Presentation] 運動神経変性疾患に共通するスプライシング経路の破たん2013

    • Author(s)
      築地仁美
    • Place of Presentation
      京都大学医学部(京都)
    • Year and Date
      2013-01-25
  • [Presentation] 遺伝性ALS モデルにおけるSIRT1 の関与2012

    • Author(s)
      永津真司、築地仁美、木下専、三澤日出巳、山中宏二
    • Organizer
      第85回日本生化学会年会
    • Place of Presentation
      福岡
    • Year and Date
      20121200
  • [Presentation] Spliceosome integrity is defective in motor neuron disease ALS and SMA2012

    • Author(s)
      Tsuiji H., Iguchi Y., Furuya A., Kataoka A., Hatsuta H., Atsuta N., Tanaka F., Hashizume Y., Akatsu H., Murayama S., Sobue G., Yamanaka K
    • Organizer
      Cold Spring Harbor Meeting : Neurodegenerative Disorders
    • Place of Presentation
      Cold Spring Harbor/NY/USA
    • Year and Date
      20121100
  • [Presentation] Spliceosome Integrity is a Common Target for Motor Neuron Disease2012

    • Author(s)
      Tsuiji H. and Yamanaka K
    • Organizer
      第35回日本神経科学大会シンポジウム : RNA 結合蛋白質と病態
    • Place of Presentation
      名古屋
    • Year and Date
      20120900
  • [Presentation] 運動神経変性疾患に共通するスプライソソーム異常2012

    • Author(s)
      築地仁美、井口洋平、古屋亜佐子、片岡礼音、村山繁雄、祖父江元、山中宏二
    • Organizer
      第14回RNA学会年会
    • Place of Presentation
      仙台(口頭発表)
    • Year and Date
      20120700
  • [Presentation] TDP-43 maintains proper U snRNA levels through association with SMN in Cajal/Gem body2012

    • Author(s)
      Tsuiji H., Iguchi Y., Furuya A., Kataoka A., Atsuta N., Tanaka F., Sobue G., Yamanaka K
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology : Protein-RNA Interaction in Biology and Disease
    • Place of Presentation
      Santa Fe, New Mexico/USA
    • Year and Date
      20120304-06
  • [Presentation] Integrity fo Spliceosome is a Common Target for Motor Neuron Disease2012

    • Author(s)
      Tsuiji H
    • Organizer
      第1回国際若手シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2012-11-17
  • [Presentation] U snRNP形成における筋萎縮性側索硬化症(ALS)原因遺伝子TDP-43 の役割2011

    • Author(s)
      築地仁美、片岡礼音、山中宏二
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜(口頭発表)
    • Year and Date
      20111200
  • [Presentation] Regulation of spliceosome by ALS-causative gene TDP-432011

    • Author(s)
      Tsuiji H., Kataoka A., Yamanaka K
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜(口頭発表)
    • Year and Date
      20110900
  • [Presentation] A Role of TDP-43 in Regulation of U snRNP Formation2011

    • Author(s)
      Tsuiji H., Kataoka A., Yamanaka K
    • Organizer
      Cold Spring Harbor Laboratory Meeting: Eukaryotic mRNA Processing
    • Place of Presentation
      Cold Spring Harbor, New York, USA
    • Year and Date
      20110823-27
  • [Presentation] A Role of TDP-43 in The Regulation of spliceosomal U snRNPs2011

    • Author(s)
      Tsuiji H., Kataoka A., Yamanaka K
    • Organizer
      The 16^<th> Annual Meeting of the RNA Society and The 13th Annual Meeting of the RNA Society of Japan
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      20110614-18

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Published: 2014-08-29   Modified: 2014-10-07  

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