Regulatory mechanism of Topoisomerase1 by small RNA molecules which leads genomic instability

• Project/Area Number: 22570169
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Kyoto University
• Principal Investigator: KOBAYASHI Maki 京都大学, 大学院・医学研究科, 准教授 (20400690)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: non-B DNA / AID / 免疫グロブリン / miRNA / 免疫グロブリン遺伝子 / DNA切断 / Non-B DNA / Topoisomerase1 / RNA編集 / 翻訳調節

Research Abstract

The molecular mechanism which suppresses Topoisomerase1 (Top1) translation in AID-dependent manner was analyzed. Involvement of miRNA, HuR and Ago2, and Ago2-binding sequence in Top1 mRNA have been realized. The putative miRNA which binds to Top1 mRNA AID-dependently will be identified very soon.

Research Products

• [Journal Article] The AID Dilemma: Infection, or Cancer? (2013)
  • Author(s): Tasuku Honjo, Maki Kobayashi, Nasim Begum, Ai Kotani, Somayeh Sabour and Hitoshi Nagaoka
  • Journal Title: Adv Cancer Res Volume: vol.113 Pages: 1-44
  • DOI: 10.1016/b978-0-12-394280-7.00001-4
  • ISBN: 9780123942807
  • Peer Reviewed
• [Journal Article] In vivo analysis of Aicda gene regulation: a critical balance between upstream enhancers and intronic silencers governs appropriate expression (2013)
  • Author(s): Le Thi Huong, Maki Kobayashi,et al
  • Journal Title: PLoSONE Volume: vol.8 Issue: 4 Pages: e61433-e61433
  • DOI: 10.1371/journal.pone.0061433
  • Peer Reviewed
• [Journal Article] In vivo analysis of Aicda gene regulation: a critical balance between upstream enhancers and intronic silencers governs appropriate expression (2013)
  • Author(s): Le Thi Huong
  • Journal Title: PLosONE Volume: 未定
  • Peer Reviewed
• [Journal Article] An evolutionary view of the mechanism for immune and genome diversity (2012)
  • Author(s): Lucia Kato, Andre Stanlie, Nasim A Begum, Maki Kobayashi, Masatoshi Aida, Tasuku Honjo
  • Journal Title: J Immunol Volume: vol. 188 Issue: 8 Pages: 3559-3566
  • DOI: 10.4049/jimmunol.1102397
  • Peer Reviewed
• [Journal Article] The AID Dilemma: Infection, or Cancer? (2012)
  • Author(s): Tasuku Honjo
  • Journal Title: Advances in Cancer Research Volume: 113 Pages: 1-44
  • Peer Reviewed
• [Journal Article] Decrease in topoisomerase I is responsible for activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (2011)
  • Author(s): Maki Kobayashi,Zahra Sabouri et al
  • Journal Title: PNAS USA Volume: vol,108 Issue: 48 Pages: 19305-19310
  • DOI: 10.1073/pnas.1114522108
  • NAID: 120003692414
  • Peer Reviewed
• [Journal Article] Preventing AID, a physiological mutator, from deleterious activation: regulation of the genomic instability that is associated with antibody diversity (2010)
  • Author(s): Hitoshi Nagaoka, Thinh Huy Tran, Maki Kobayashi, M a s a t o s h i A i d a a n d T a s u k u H o n j o
  • Journal Title: International Immunology Volume: vol 22 Issue: 4 Pages: 227-235
  • DOI: 10.1093/intimm/dxq023
  • NAID: 10027391988
• [Journal Article] Preventing AID, a physiological mutator, from deleterious activation : regulation of the genomic instability that is associated with antibody diversity (2010)
  • Author(s): Hitoshi Nagaoka, Thinh Huy Tran, Maki Kobayashi, Masatoshi Aida, Tasuku Honjo.
  • Journal Title: International Immunology Volume: 22 Pages: 227-235
  • NAID: 10027391988
• [Presentation] Activation-induced cytidine deaminase regulates Topoisomerase1 protein by miRNA during immnoglobulin gene recombination (2013)
  • Author(s): Maki Kobayashi et al
  • Organizer: Keystone Meeting, Noncoding RNAs in Development and Cancer
  • Place of Presentation: Fairmont Hotel Vancouver
  • Year and Date: 2013-01-22
• [Presentation] Activation-induced cytidine deaminase regulates Topoisomerase1 protein by miRNA during immnoglobulin gene recombination (2012)
  • Author(s): Maki Kobayashi et al
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2012-12-14
• [Presentation] Activation-induced cytidine deaminase regulates Topoisomerase1 protein by miRNA during immnoglobulin gene recombination (2012)
  • Author(s): Maki Kobayashi et al
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2012-12-06
• [Presentation] AID-induced Ago2 binding to the 3' UTR of Topoisomerase I (Top1) mRNA is associated with Top1 decrease, which is responsible for somatic hypermutation and class switch recombination (2012)
  • Author(s): M Kobayashi, J Xu, Z Sabouri, S Sabouri,Y Kitawaki, Y Sasaki, Y Pommier, T Honjo
  • Organizer: Keystone Symposia - Mutations, Malignancy and Memory - Antibodies and Immunity (C6)
  • Place of Presentation: ボストンパークプラザホテル
  • Year and Date: 2012-03-19
• [Presentation] AID-induced Ago2 binding to the 3' UTR of Topoisomerase I (Top1) mRNA is associated with Top1 decrease, which is responsible for somatic hypermutation and class switch (2012)
  • Author(s): M Kobayashi, J Xu, Z Sabouri, S Sabouri, Y Kitawaki, Y Sasaki, Y
  • Organizer: Keystone Symposia-Mutations, Malignancy and Memory-Antibodies and Immunity (C6)
  • Place of Presentation: ボストンパークプラザホテル
  • Year and Date: 2012-03-19
• [Presentation] Decrease in topoisomerase I is responsible for AID-dependent somatic hypermutation (2011)
  • Author(s): Maki Kobayashi1, Zahra Sabouri1, Somayeh Sabouri1 and Tasuku Honjo
  • Organizer: 第23回日本分子生物学会、シンポジウム「ゲノムダイナミクス」
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] AID-induced Topoisomerase1 reduction regulates somatic hypermutation frequency (2011)
  • Author(s): Maki Kobayashi, Zahra Sabouri, Masatoshi Aida, Yoko Kitawaki, and Tasuku Honjo
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] Begum and Tasuku Honjo. AID-induced decrease in topoisomerase1 induces DNA structural alteration and DNA cleavage for class switch r e c o m b i n a t i o n (2010)
  • Author(s): Maki Kobayashi, Masatoshi Aida, Hitoshi Nagaoka, Nasim A
  • Organizer: C o l d S p r i n g H a r b o r Meeting on Gene expression and signaling in the immune system
  • Place of Presentation: Cold Spring Harbor, New York
• [Presentation] Epigenetic regulationof S region chromatin is essential to AID-induced S region DNA cleavage by topoisomerase 1 (2010)
  • Author(s): Maki Kobayashi, M a s a t o s h i A i d a , A n d r e Stanlie, Nasim A. Begum, Hitoshi Nagaoka and Tasuku Honjo
  • Organizer: International AID workshop: from Immune Diversification to Cancer
  • Place of Presentation: Stockholm、Sweden
• [Presentation] Topoisomerase1 regulates AID-induced DNA cleavage (2010)
  • Author(s): Maki Kobayashi, Zahra Sabouri, Masatoshi Aida, Yoko Kitawaki, and Tasuku Honjo
  • Organizer: 14thInternational congress of immunology
  • Place of Presentation: 神戸
• [Presentation] Transcription Factors Sox13 Regulates the Hematopoietic Expression of GATA2 in Vertebrate Embryos (2010)
  • Author(s): Maki Kobayashi-Osaki, Makoto Kobayashi, Miki Takeuchi and Masayuki Yamamoto
  • Organizer: 9th Japanese Biochemical Society Bio-Frontier Symposium 2010, 5th International Symposium on GATA factors
  • Place of Presentation: 仙台
• [Presentation] Topoisomerase1 regulates AID-induced DNA cleavage (2010)
  • Author(s): Maki Kobayashi, Somayeh Sabouri, Zahra Sabouri, Yoko Kitawaki, and Tasuku Honjo
  • Organizer: Biochemistry and Molecular Biology2010
  • Place of Presentation: 神戸
• [Presentation] AID-induced decrease in topoisomerase1 induces DNA structural alteration and DNA cleavage for class switch recombination. (2010)
  • Author(s): Maki Kobayashi, Masatoshi Aida, Hitoshi Nagaoka, Nasim A.Begum, Tasuku Honjo.
  • Organizer: Cold Spring Harbor Meeting on Gene expression and signaling in the immune system
  • Place of Presentation: Cold Spring Harbor, New York.
• [Presentation] Epigenetic regulation of S region chromatin is essential to AID-induced S region DNA cleavage by topoisomerase 1. (2010)
  • Author(s): Maki Kobayashi, Masatoshi Aida, Andre Stanlie, Nasim A.Begum, Hitoshi Nagaoka, Tasuku Honjo.
  • Organizer: International AID workshop : from Immune Diversification to Cancer
  • Place of Presentation: Stockholm Sweden(招待講演)
• [Presentation] Topoisomerase1 regulates AID-induced DNA cleavage. (2010)
  • Author(s): Maki Kobayashi, Zahra Sabouri, Masatoshi Aida, Yoko Kitawaki, Tasuku Honjo.
  • Organizer: 14^<th> International congress of immunology
  • Place of Presentation: 神戸
• [Presentation] Transcription Factors Sox13 Regulates the Hematopoietic Expression of GATA2 in Vertebrate Embryos. (2010)
  • Author(s): Maki Kobayashi-Osaki, Makoto Kobayashi, Miki Takeuchi, Masayuki Yamamoto.
  • Organizer: 9th Japanese Biochemical Society Bio-Frontier Symposium 2010, 5th International Symposium on GATA factors.Sendai
  • Place of Presentation: 仙台
• [Presentation] Topoisomerase1 regulates AID-induced DNA cleavage. (2010)
  • Author(s): Maki Kobayashi, Somayeh Sabouri, Zahra Sabouri, Yoko Kitawaki, Tasuku Honjo.
  • Organizer: Biochemistry and Molecular Biology2010
  • Place of Presentation: 神戸