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Defective RNA metabolism in motor neurons from Amyotrophic Lateral Scelosis patients

Research Project

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
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsALS / spliceosome / snRNP / TDP-43 / RNA / スプライソソーム / snRNA / SMN / SMA / FUS / RNA代謝 / 筋萎縮性側索硬化症 / 脊髄性筋萎縮症 / splicing
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.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (24 results)

All 2013 2012 2011 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (20 results) (of which Invited: 1 results) Remarks (2 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

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Spliceosome integrity is defective in the motor neuron diseases 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 Mol Med

      Volume: 5 Issue: 2 Pages: 221-234

    • DOI

      10.1002/emmm.201202303

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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)
    • Related Report
      2012 Final Research Report
  • [Presentation] Spliceosome Integrity is a Common Target for Motor Neuron Disease2012

    • Author(s)
      Hitomi Tsuiji
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場、名古屋
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Spliceosome integrity is defective in motor neuron disease ALS and SMA.2012

    • Author(s)
      Hitomi Tsuiji
    • Organizer
      Cold Spring Harbor Meeting: Neurodegenerative Disorders
    • Place of Presentation
      Cold Spring Harbor laboratory, Cold Spring Harbor, NY, USA
    • Related Report
      2012 Annual Research Report
  • [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
    • Organizer
      第14回RNA学会年会
    • Place of Presentation
      東北大学、仙台
    • Related Report
      2012 Annual Research Report
  • [Presentation] TDP-43 in U snRNP regulation2012

    • Author(s)
      Tsuiji H., Kataoka A., Yamanaka K.
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology: Neurodegenerative Diseases: The Molecular and Cellular Basis for Neurodegeneration (F2)
    • Place of Presentation
      Taos, New Mexico, USA
    • Related Report
      2011 Research-status Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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)
    • Related Report
      2012 Final Research Report
  • [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)
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2011 Research-status Report
  • [Presentation] Regulation of spliceosome by ALS-causative gene TDP-432011

    • Author(s)
      築地仁美、片岡礼音、山中宏二
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [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
    • Related Report
      2011 Research-status Report
  • [Presentation] A Role of TDP-43 in The Regulation of spliceosomal U snRNPs2011

    • Author(s)
      Tsuiji H., Kataoka A., Yamanaka K.
    • Organizer
      The 16th Annual Meeting of the RNA Society and The 13th Annual Meeting of the RNA Society of Japan
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2011 Research-status Report
  • [Presentation] Integrity fo Spliceosome is a Common Target for Motor Neuron Disease.

    • Author(s)
      Hitomi Tsuiji
    • Organizer
      第1回国際若手シンポジウム
    • Place of Presentation
      京都平安ホテル、京都
    • Related Report
      2012 Annual Research Report
  • [Remarks] プレスリリース

    • URL

      http://www.riken.jp/pr/press/2013/20130125_1/

    • Related Report
      2012 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://mnd.brain.riken.jp/index.html

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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