The pathogenesis of GEM bodies reduction in ALS affected tissues.

• Project/Area Number: 25860703
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Niigata University
• Principal Investigator: ISHIHARA Tomohiko 新潟大学, 脳研究所, 助教 (70612232)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ALS / U snRNAs / GEM小体 / スプライシング / TDP-43 / GEM / SMN / snRNAs / GEM body

Outline of Final Research Achievements

Our object is the elucidation of ALS pathogenesis. We have already found the reduction of minor spliceosomal U snRNA and GEM bodies in ALS affected tissues. U snRNA is main component of the splicing machinery and GEM bodies have important role in the maturation of U snRNAs. We intended to clarify the pathogenesis of GEM bodies reduction and aberrant splicing in ALS affected tissues.　In this study, we found the reduction of SMN mRNA in TDP-43 depleted cells. SMN protein is main component of GME bodies. And there were minor spliceosome dependent splicing aberrations in ALS affected tissues.

Research Products

• [Journal Article] Aberration of the spliceosome in amyotrophic lateral sclerosis (2014)
  • Author(s): Ishihara T, Onodera O.et al.
  • Journal Title: 臨床神経学 Volume: 54 Pages: 1155-7
  • Open Access
• [Journal Article] Minor splicing pathway is not minor any more: Implications for thepathogenesis of motor neuron diseases. (2014)
  • Author(s): Onodera O，Ishihara T, Shiga A, Nishizawa M, et.al.
  • Journal Title: Neuropathology. Volume: 1 Pages: 99-107
  • Peer Reviewed
• [Journal Article] Decreased number of Gemini of coiled bodies and U12 snRNA levelin amyotrophic lateral sclerosis． (2013)
  • Author(s): Ishihara T, Ariizumi Y, Shiga A, Onodera O， et.al.
  • Journal Title: Hum Mol Genet． Volume: 20 Pages: 4136-47
  • Peer Reviewed
• [Presentation] The reduction of minor spliceosome and aberrant splicing in ALS. (2014)
  • Author(s): 石原 智彦
  • Organizer: Cell symposia Regulatory RNAｓ
  • Place of Presentation: バークリー（USA)・Claremont Hotel & Spa
  • Year and Date: 2014-10-21
• [Presentation] ALSにおけるspliceosome異常 （シンポジウム発表） (2014)
  • Author(s): 石原 智彦
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡，福岡国際会議場
  • Year and Date: 2014-05-24
  • Invited
• [Presentation] ALSでのStasimonヒトホモログ mRNAのスプライシング異常の検討 (2014)
  • Author(s): 石原 智彦
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡，福岡国際会議場
  • Year and Date: 2014-05-21
• [Presentation] Reduction of U11/U12 small nuclear ribonucleoprotein in amyotrophic lateral sclerosis (2013)
  • Author(s): 石原 智彦
  • Organizer: the 24th International Symposium on ALS/MND
  • Place of Presentation: ミラノ, イタリア
• [Presentation] ALS患者神経組織におけるU12 snRNAの減少とスプライシング異常
  • Author(s): 石原 智彦
  • Organizer: 第５４回日本神経学会学術大会
  • Place of Presentation: 東京，日本
• [Book] 新領域別症候群27 神経症候群II (2014)
  • Author(s): 酒井 直子，石原 智彦，小野寺 理，西澤 正豊
  • Total Pages: 5
  • Publisher: 日本臨床社