The expression and effects of aberrant RNAs in repeat expansion disorders

• Project/Area Number: 19790620
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KINO Yoshihiro The Institute of Physical and Chemical Research, 構造神経病理研究チーム, 研究員 (80415140)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: リピート伸長疾患 / RNA代謝 / ハンチントン病 / CTGリピート / リピート伸長 / 神経変性 / 選択的スプライシング / 筋強直性ジストロフィー / RNA結合タンパク質 / junctophilin-3 / ポリアミノ酸 / 神経変性疾患 / ポリアラニン

Research Abstract

ハンチントン病(HD)などのCAGリピート伸長疾患では、伸長した異常タンパク質が毒性をもたらす。一方、伸長した非コード領域のリピートRNAが毒性をもたらす例もある。これらの発症機構を考える上で、Huntington's disease-like 2(HDL2)は興味深い。HDL2は非コード領域にもコード領域にもなるCTGリピート伸長を原因としてHD様の症状を示す神経変性疾患である。本研究では、HDL2原因遺伝子のJPH3の解析を行い、その遺伝子産物の特性や制御因子を明らかにした。

Research Products

• [Journal Article] MBNL1 associates with YB-1 in cytoplasmic stress granules (2008)
  • Author(s): 大西隼、紀嘉浩、森田智子、二井勇人、笹川昇、石浦章一
  • Journal Title: Journal of Neuroscience Research 86(9) Pages: 1994-2002
  • Peer Reviewed
• [Journal Article] Quantitative analysis of CUG-BP1 binding to RNA repeats (2008)
  • Author(s): 森大輔、笹川昇、紀嘉浩、石浦章一
  • Journal Title: Journal of Biochemistry 143(3) Pages: 377-383
  • NAID: 10024908854
  • Peer Reviewed
• [Journal Article] Expression of polyalanine stretches inducesmitochondrial dysfunction (2008)
  • Author(s): 鳥海和也、大間陽子、紀嘉浩、二井勇人、笹川昇、石浦章一
  • Journal Title: Journal of Neuroscience Research 86(7) Pages: 1529-1537
  • Peer Reviewed
• [Journal Article] MBNL1 associates with YB-1 in cytoplasmic stress granules (2008)
  • Author(s): Onishi, et al.
  • Journal Title: Journal of Neuroscience Research 86(9) Pages: 1994-2002
  • Peer Reviewed
• [Journal Article] Expression of polyalanine stretches induces mitochondrial dysfunction (2008)
  • Author(s): Toriumi, et al.
  • Journal Title: Journal of Neuroscience Research 86(7) Pages: 1529-1537
  • Peer Reviewed
• [Journal Article] Quantitative analysis of CUG-BP1 binding to RNA repeats (2008)
  • Author(s): Mori, et al.
  • Journal Title: Journal of Biochemistry 143(3) Pages: 377-383
  • Peer Reviewed
• [Journal Article] Interactions between homopolymeric amino acids (HPAAs) (2007)
  • Author(s): 大間陽子、紀嘉浩、鳥海和也、笹川昇、石浦章一
  • Journal Title: Protein Science 16(10) Pages: 2195-2204
  • Peer Reviewed
• [Journal Article] Expression of MBNL and CELF mRNA transcripts in muscles with myotonic dystrophy (2007)
  • Author(s): 根津友理子、紀嘉浩、笹川昇、西野一三、石浦章一
  • Journal Title: Neuromuscular Disorder 17(4) Pages: 306-312
  • Peer Reviewed
• [Journal Article] Interactions between homopolymeric amino acids(HPAAs) (2007)
  • Author(s): Oma, et. al.
  • Journal Title: Protein Science 16(10) Pages: 2195-2204
  • Peer Reviewed
• [Journal Article] Expression of MBNL and CELF mRNA transcripts in muscles with myotonic dystrophy (2007)
  • Author(s): Nezu, et. al.
  • Journal Title: Neuromuscular Disorders 17(4) Pages: 306-312
  • Peer Reviewed
• [Presentation] Cell-based analysis of splicing regulation by MBNL proteins (2008)
  • Author(s): 紀嘉浩
  • Organizer: Therapeutic Strategies for Myotonic Dystrophy Workshop
  • Place of Presentation: バンフ(カナダ)
  • Year and Date: 2008-08-15
• [Presentation] Cell-based analysis of splicing regulation by MBNL proteins (2008)
  • Author(s): 紀嘉浩
  • Organizer: Therapeutic Strategies for Myotonic Dystrophy Workshop
  • Place of Presentation: カナダ、バンフ
  • Year and Date: 2008-08-15
• [Presentation] Structural determinants for the molecular properties of MBNL proteins (2007)
  • Author(s): 紀嘉浩(代表者)
  • Organizer: 6th International Myotonic Dystrophy Consortium Meeting
  • Place of Presentation: ミラノ(イタリア)
  • Year and Date: 2007-09-14
• [Presentation] Structural determinants for the molecular properties of MBNL proteins (2007)
  • Author(s): Yoshihiro Kino, et. al.
  • Organizer: 6th Internation Myotonic Dystrophy Consortium Meeting
  • Place of Presentation: ミラノ(イタリア)
  • Year and Date: 2007-09-14
• [Book] 実験医学 (増刊) 脳神経疾患の分子病態と治療への展開 「神経筋疾患とRNA代謝異常」 (2007)
  • Author(s): 紀嘉浩、貫名信行
  • Publisher: 羊土社