Autoimmune diseases and RNA modifications: Molecular mechanism of pathogenesis of systemic lupus erythematosus.

• Project/Area Number: 20200070
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Molecular biology; 膠原病・アレルギー・感染症内科学
• Research Institution: University of Miyazaki
• Principal Investigator: UECHI Tamayo 宮崎大学, フロンティア科学実験総合センター, 研究員 (10381104)
• Co-Investigator(Kenkyū-buntansha): TAKAYANAGI Atsushi 慶応義塾大学, 医学部, 講師 (80245464) ; TAKAMI Yasunari 宮崎大学, 医学部, 准教授 (80236356) ; HIGA Sayomi 琉球大学, 医学研究科, 助教 (20381105)
• Co-Investigator(Renkei-kenkyūsha): KENMOCHI Naoya 宮崎大学, フロンティア科学実験総合センター, 教授 (00133124)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥32,630,000 (Direct Cost: ¥25,100,000、Indirect Cost: ¥7,530,000); Fiscal Year 2010: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000); Fiscal Year 2009: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000); Fiscal Year 2008: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
• Keywords: RNA修飾 / 自己免疫疾患 / 人工抗体 / SLE / ゼブラフィッシュ / モルフォリノアンチセンスオリゴ / ノンコーディングRNA / ファージディスプレイ / 人工杭体

Research Abstract

A majority of non-coding RNAs undergo posttranscriptional modifications. Lack of such modifications might lead to autoimmune response. To investigate the possible mechanism of pathogenesis, we isolated recombinant anti-RNA antibodies that can bind to the modification sites related to patient autoantibodies. We also developed a zebrafish model of defective rRNA modifications and demonstrated that loss of rRNA modification, even at a single site, have deleterious effects on early development in vertebrates.

Research Products

• [Journal Article] Loss of ribosomal RNA modification causes developmental defects in zebrafish (2012)
  • Author(s): Higa-Nakamine S, Suzuki T, Uechi T, Chakraborty A, Nakajima Y, Nakamura M, Hirano N, Suzuki T, Kenmochi N
  • Journal Title: Nucleic Acids Res Volume: 40 Pages: 391-398
  • Peer Reviewed
• [Journal Article] Screening of scFv-displaying phages recognizing distinct extracellular domains of EGF receptor by target-guided proximity labeling method. (2011)
  • Author(s): Chang C, Takayanagi A, Yoshida T, Shimizu N.
  • Journal Title: J Immunol Methods Volume: 372 Pages: 127-136
  • Peer Reviewed
• [Journal Article] Loss of ribosomal RNA modification causes developmental defects in zebrafish (2011)
  • Author(s): Sayomi Higa-Nakamine
  • Journal Title: Nucleic Acids Rresearch Volume: 40 Pages: 391-398
  • Peer Reviewed
• [Journal Article] Screening of scFv-displaying phages recognizing distinct extracellular domains of EGF receptor by target-guided proximity labeling method (2011)
  • Author(s): Cialun Chang
  • Journal Title: Journal of Immunological Methods Volume: 372 Pages: 127-136
  • Peer Reviewed
• [Journal Article] ゼブラフィッシュにおけるRNA修飾の機能解析. (2009)
  • Author(s): 比嘉三代美, 剣持直哉
  • Journal Title: 蛋白質核酸酵素：mRNAプログラム Volume: 54 Pages: 2092-2097
• [Journal Article] リボソーム病：翻訳装置のシステム障害 (2009)
  • Author(s): 上地珠代, 剣持直哉.
  • Journal Title: 遺伝子医学MOOK：最新RNAと疾患研究 Volume: 15 Pages: 79-84
• [Journal Article] Loss of ribosomal protein L11 affects zebrafish embryonic development through a p53-dependent apoptotic response (2009)
  • Author(s): Chakraborty A, Uechi T, Higa S, Torihara H, Kenmochi N
  • Journal Title: PLoS ONE. Volume: 4
  • NAID: 120007123103
  • Peer Reviewed
• [Journal Article] リボソーム病:翻訳装置のシステム障害 (2009)
  • Author(s): 上地珠代
  • Journal Title: 遺伝子医学MOOK:最新RNAと疾患研究 15 Pages: 79-84
• [Journal Article] ゼブラフィッシュにおけるRNA修飾の機能解析 (2009)
  • Author(s): 比嘉三代美
  • Journal Title: 蛋白質核酸酵素:mRNAプログラム 54 Pages: 2092-2097
• [Journal Article] Deficiency of ribosomal protein S19 during early embryogenesis leads to reduction of erythrocytes in a zebrafish model of Diamond-Blackfan anemia. (2008)
  • Author(s): Uechi T, Nakajima Y, Chakraborty A, Torihara H, Higa S, Kenmochi N.
  • Journal Title: Hum Mol Genet Volume: 17 Pages: 3204-3211
  • NAID: 120007123102
  • Peer Reviewed
• [Journal Article] Construction and characterization of single-chain antibodies against human insulin-like growth factor-I receptor from hybridomas producing 1H7 or 3B7 monoclonal antibody (2008)
  • Author(s): Kusada Y, Morizono T, Matsumoto-Takasaki A, Sakai K, Sato S, Asanuma H, Takayanagi A, Fujita-Yamaguchi Y.
  • Journal Title: J Biochem Volume: 143 Pages: 9-19
  • NAID: 10024907273
  • Peer Reviewed
• [Journal Article] Deficiency of ribosomal protein S19 during early embryogenesis leads to reduction of erythrocytes in a zebrafish model of Diamond-Blackfan anemia (2008)
  • Author(s): Tamayo Uechi
  • Journal Title: Human Molecular Genetics 17 Pages: 3204-3211
  • Peer Reviewed
• [Journal Article] Construction and characterization of single-chain antibodies against human insulin-like growth factor-I receptor from hybridomas. producing 1H7 or 3B7 monoclonal antibody (2008)
  • Author(s): Yu Kusada
  • Journal Title: The Journal of Biochemistry 143 Pages: 9-19
  • Peer Reviewed
• [Journal Article] イントロン内在型機能性RNA遺伝子の進化 (2008)
  • Author(s): 剣持直哉
  • Journal Title: 生体の科学 59 Pages: 386-387
• [Presentation] Loss of snoRNA expression impairs ribosomal RNA modification andcauses developmental defects in zebrafish. (2012)
  • Author(s): Kenmochi N.
  • Organizer: Protein-RNA Interactions in Biology and Disease.
  • Place of Presentation: サンタフェ, 米国.
  • Year and Date: 2012-03-05
• [Presentation] Loss of snoRNA expression impairs ribosomal RNA modification and causes developmental defects in zebrafish (2012)
  • Author(s): Naoya Kenmochi
  • Organizer: Protein-RNA Interactions in Biology and Disease
  • Place of Presentation: サンタフェ、米国(招待講演)
  • Year and Date: 2012-03-05
• [Presentation] 人工抗体ライブラリーを用いた抗RNA抗体の作製 (2011)
  • Author(s): 剣持直哉
  • Organizer: BioJapan2011
  • Place of Presentation: 横浜.
  • Year and Date: 2011-10-07
• [Presentation] ゼブラフィッシュをモデルとしたリボソーム病発症の分子機構の解析 (2011)
  • Author(s): 剣持直哉
  • Organizer: 日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-22
• [Presentation] Defective erythropoiesis and ribosomal dysfunction in zebrafish model of Diamond-Blackfan anemia (2011)
  • Author(s): Uechi T.
  • Organizer: RNA Society Meeting "RNA 2011 Kyoto".
  • Place of Presentation: 京都
  • Year and Date: 2011-06-14
• [Presentation] 造血異常を引き起こすリボソームの翻訳調節機構の解析 (2010)
  • Author(s): 上地珠代
  • Organizer: 日本RNA学会年会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-08
• [Presentation] Ribosomal dysfunction and bone marrow failure: Analysis of zebrafish model for Diamond-Blackfan anemia. (2010)
  • Author(s): Uechi T.
  • Organizer: 15th Annual Meeting of the RNA Society.
  • Place of Presentation: シアトル, 米国
  • Year and Date: 2010-06-24
• [Presentation] snoRNA遺伝子とイントロンの進化 (2009)
  • Author(s): 剣持直哉
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] snoRNAの機能阻害によるリボソームRNA修飾の機能解析 (2009)
  • Author(s): 比嘉三代美
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] snoRNAの機能阻害によるリボソームRNA修飾の機能解析 (2009)
  • Author(s): 比嘉三代美
  • Organizer: 日本分子生物学会.
  • Place of Presentation: 横浜
  • Year and Date: 2009-08-30
• [Presentation] Loss of ribosomal protein s19 leadsto defective erythropoiesis in a zebrafish model of Diamond-Blackfan anemia. (2009)
  • Author(s): Uechi T.
  • Organizer: Ribosomal Synthesis
  • Place of Presentation: レーゲンスブルグ, ドイツ
  • Year and Date: 2009-08-30
• [Presentation] Loss of ribosomal protein s19 leads to defective erythropoiesis in a zebrafish model of Diamond-Blackfan anemia (2009)
  • Author(s): 上地珠代
  • Organizer: Ribosomal Synthesis
  • Place of Presentation: レーゲンスブルグ,ドイツ
  • Year and Date: 2009-08-30
• [Presentation] Functional analysis of rRNA modification enzyme dyskerin in zebrafish : A vertebrate model for Dyskeratosis Congenita (2009)
  • Author(s): 平野菜穂子
  • Organizer: Ribosomal Synthesis
  • Place of Presentation: レーゲンスブルグ,ドイツ
  • Year and Date: 2009-08-28
• [Presentation] RNA修飾酵素の機能解析：ゼブラフィッシュを用いた疾患モデルの作製. (2009)
  • Author(s): 比嘉三代美.
  • Organizer: 日本RNA学会
  • Place of Presentation: 新潟
  • Year and Date: 2009-07-28
• [Presentation] 造血異常とリボソームタンパク質遺伝子の変異:ゼブラフィッシュを用いた解析 (2009)
  • Author(s): 上地珠代
  • Organizer: 日本RNA学会
  • Place of Presentation: 新潟
  • Year and Date: 2009-07-28
• [Presentation] RNA修飾酵素の機能解析:ゼブラフィッシュを用いた疾患モデルの作製 (2009)
  • Author(s): 比嘉三代美
  • Organizer: 日本RNA学会
  • Place of Presentation: 新潟
  • Year and Date: 2009-07-28
• [Presentation] ゼブラフィッシュを用いたRNA修飾の機能解析 (2008)
  • Author(s): 平野菜穂子
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] ゼブラフィッシュを用いたsnoRNAの生成阻害とRNA修飾の役割 (2008)
  • Author(s): 比嘉三代美.
  • Organizer: 日本RNA学会
  • Place of Presentation: 札幌
  • Year and Date: 2008-07-23
• [Book] 機能性RNAの分子生物学 The molecular biology of non-coding RNA,【4章】真核生物のsmall RNA,(111-150) (2010)
  • Author(s): 剣持直哉.
  • Publisher: クバプロ
• [Patent(Industrial Property Rights)] 抗RNA抗体のスクリーニング方法 (2011)
  • Inventor(s): 剣持直哉, 吉浜麻生, 高柳淳, 清水信義.
  • Industrial Property Rights Holder: 宮崎大学, 慶應義塾
  • Filing Date: 2011-04-26
• [Patent(Industrial Property Rights)] 抗RNA抗体のスクリーニング方法 (2011)
  • Inventor(s): 剣持直哉、吉浜麻生、高柳淳、清水信義
  • Industrial Property Rights Holder: 宮崎大学、慶應義塾
  • Industrial Property Number: 2011-098698
  • Filing Date: 2011-04-26