Roles of an RNA-binding protein MBNL1 in polyglutamine diseases

• Project/Area Number: 21790854
• 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): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: RNA結合タンパク質 / 神経変性疾患 / MBNL1 / CAGリピート / 筋強直性ジストロフィー / 選択的スプライシング / ポリグルタミン

Research Abstract

In CAG repeat expansion diseases including Huntington's disease, mutant proteins with an expanded polyglutamine tract are thought to have toxic effects in the cells. It is also possible that expanded CAG repeat RNA has toxicity in these diseases. MBNL1 is an RNA-binding protein that interacts with expanded CAG repeat RNA and can be involved in the RNA metabolisms of diseases caused by CAG/CTG repeat expansion. This study identified the effects of MBNL1 on the metabolisms of mutant RNA associated with repeat expansion diseases.

Research Products

• [Journal Article] Intracellular localization and splicing regulation of FUS/TLS are variably affected by amyotrophic lateral sclerosis-linked mutations. (2011)
  • Author(s): Kino Y, Washizu C, Aquilanti E, Okuno M, Kurosawa M, Yamada M, Doi H, Nukina N.
  • Journal Title: Nucleic Acids Research 39(7) Pages: 2781-2798
  • Peer Reviewed
• [Journal Article] Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein. (2010)
  • Author(s): Bauer PO, Goswami A, Wong HK, Okuno M, Kurosawa M, Yamada M, Miyazaki H, Matsumoto G, Kino Y, Nagai Y, Nukina N.
  • Journal Title: Nature Biotechnologyz 28 Pages: 256-263
  • Peer Reviewed
• [Journal Article] Intracellular localization and splicing regulation of FUS/TLS are variably affected by amyotrophic lateral sclerosis-linked mutations. (2010)
  • Author(s): Kino, et al.
  • Journal Title: Nucleic Acids Research
  • Peer Reviewed
• [Journal Article] Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein. (2010)
  • Author(s): Bauer, et al.
  • Journal Title: Nature Biotechnology Volume: 28 Pages: 256-263
  • Peer Reviewed
• [Journal Article] MBNL and CELF proteins regulate alternative splicing of the skeletal muscle chloride channel CLCN1. (2009)
  • Author(s): Kino Y, Washizu C, Oma Y, Onishi H, Nezu Y, Sasagawa N, Nukina N, Ishiura S.
  • Journal Title: Nucleic Acids Research 37(19) Pages: 6477-6490
  • Peer Reviewed
• [Journal Article] RNAi screening in Drosophila cells identifies new modifiers of mutant huntingtin aggregation. (2009)
  • Author(s): Doumanis J, Wada K, Kino Y, Moore AW, Nukina N.
  • Journal Title: PLoS One 4(9)
  • Peer Reviewed
• [Journal Article] Inhibition of Rho kinases enhances the degradation of mutant huntingtin. (2009)
  • Author(s): Bauer PO, Wong HK, Oyama F, Goswami A, Okuno M, Kino Y, Miyazaki H, Nukina N.
  • Journal Title: Journal of Biological Chemistry 284(19) Pages: 13153-13164
  • Peer Reviewed
• [Journal Article] MBNL and CELF proteins regulate alternative splicing of the skeletal muscle chloride channel CLCN1 (2009)
  • Author(s): Kino et al.
  • Journal Title: Nucleic Acids Research 37(19) Pages: 6477-6490
  • Peer Reviewed
• [Journal Article] RNAi screening in Drosophila cells identifies new modifiers of mutant huntingtin aggregation (2009)
  • Author(s): Doumanis et al.
  • Journal Title: PLoS One 4(9)
  • Peer Reviewed
• [Journal Article] Inhibition of Rho kinases enhances the degradation of mutant huntingtin (2009)
  • Author(s): Bauer et al.
  • Journal Title: Journal of Biological Chemistry 284(19) Pages: 13153-13164
  • Peer Reviewed
• [Presentation] The effects of ALS-linked mutations of FUS/TLS第1回新潟大学脳研究所共同研究拠点国際シンポジウム (2010)
  • Author(s): Kino, et al.
  • Organizer: Current Understandings and Future Directions for ALS
  • Place of Presentation: 新潟
  • Year and Date: 2010-11-22
• [Presentation] The effects of ALS-linked mutations of FUS/TLS (2010)
  • Author(s): Kino, et al.
  • Organizer: 第1回新潟大学脳研究所共同研究拠点国際シンポジウムCurrent Understandings and Future Directions for ALS
  • Place of Presentation: 新潟
  • Year and Date: 2010-11-22
• [Presentation] RNA結合タンパク質TLS/FUSの機能と神経変性疾患との関連 (2010)
  • Author(s): Kino, et al.
  • Organizer: 包括脳ネットワーク夏のワークショップ
  • Place of Presentation: 札幌
  • Year and Date: 2010-07-28
• [Presentation] RNA結合タンパク質TLS/FUSの機能と神経変性疾患との関連 (2010)
  • Author(s): Kino, et al.
  • Organizer: 包括脳ネットワーク 夏のワークショップ
  • Place of Presentation: 札幌
  • Year and Date: 2010-07-28
• [Presentation] Intracellular localization and splicing regulation of FUS/TLS are variably affected by amyotrophic lateral sclerosis-linked mutations. (2010)
  • Author(s): Kino, et al.
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 神戸
• [Presentation] Intracellular localization and splicing regulation of FUS/TLS are variably affected by amyotrophic lateral sclerosis-linked mutations. (2010)
  • Author(s): Kino, et al.
  • Organizer: 第33回日本分子生物学会年会 第83回日本生化学会大会 合同大会(BMB2010)
  • Place of Presentation: 神戸
• [Presentation] 疾患に関連したMBNL1のスプライシング制御 (2009)
  • Author(s): 紀嘉浩
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] Autoregulation of MBNL1 : coupling of splicing regulatory activity and intracellular localization (2009)
  • Author(s): 紀嘉浩
  • Organizer: 7th International Myotonic Dystrophy Consortium Meeting
  • Place of Presentation: ヴュルツブルク(ドイツ)
  • Year and Date: 2009-09-10