Studies on the physiological functions of DExD/H RNA helicase family

• Project/Area Number: 18209015
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Kyoto University
• Principal Investigator: FUJITA Takashi Kyoto University, ウイルス研究所, 教授 (10156870)
• Co-Investigator(Kenkyū-buntansha): YONEYAMA Mitsutoshi 京都大学, ウイルス研究所, 准教授 (40260335)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥48,750,000 (Direct Cost: ¥37,500,000、Indirect Cost: ¥11,250,000); Fiscal Year 2008: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000); Fiscal Year 2007: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2006: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
• Keywords: 免疫学 / ウイルス / インターフェロン / RNA / ヘリカーゼ / 炎症 / サイトカイン / 自然免疫 / 二重鎖RNA / マイクロRNA / ノックアウトマウス / 発生制御 / トランジェニックマウス / トランスジェニックマウス

Research Abstract

DExD/H RNAヘリカーゼファミリーが細胞内で複製するウイルスのセンサーとして機能し、抗ウイルス自然免疫反応を誘導することを見出した。このセンサーとしての機能は、ウイルスの複製の結果生じる特異的な構造のRNAを認識するためであることを明らかにした。また構造生物学的な解析によって比較的小さな、カルボキシル末端側のドメインがこの認識に深く関わっていることを明らかにした。

Research Products

• [Journal Article] Solution Structures of MDA5 and LGP2 C-terminal Domains: Identification of the RNA Recognition Loop in RIG-I Like Receptors (2009)
  • Author(s): Takahasi, K., Kumeta, H., Tsuduki, N., Narita, R., Shigemoto, T., Hirai, R., Yoneyama, M., Horiuchi, M., Ogura, K., Fujita, TT., Inagaki, F.
  • Journal Title: J. Biol. Chem(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Identification of loss of function mutations in human genes encoding RIG-I and mda5 : Implications for resistance to type I diabetes (2009)
  • Author(s): Shigemoto, T., Kageyama, M., Hirai, R., Zheng, J-P., Yoneyama, M., Fujita, T.
  • Journal Title: J. Biol. Chem(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Solution Structures of MDA5 and LGP2 C-terminal Domains : Identification of the RNA Recognition Loop in RIG-I Like Receptors (2009)
  • Author(s): Takahasi, K., Kumeta, H., Tsuduki, N., Narita, R., Shigemoto, T., Hirai, R., Yoneyama, M., Horiuchi, M., Ogura, K., Fujita, T., Inagaki, F.
  • Journal Title: J, Biol. Chem
  • Peer Reviewed
• [Journal Article] Identification of loss of function mutations in human genes encoding RIG-I and mda5 : Implications for resistance to type I diabetes (2009)
  • Author(s): Shigemoto, T., Kageyama, M., Hirai, R., Zheng, J-P., Yoneyama, M., Fujita, T.
  • Journal Title: J. Biol. Chem
  • Peer Reviewed
• [Journal Article] Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5 (2008)
  • Author(s): Kato, H., Takeuchi, O., Mikamo-Satoh, E., Hirai, R., Kawai, T., Matsushita, K., Hiiragi, A., Dermody, TS., Fujita, T., Akira, S.
  • Journal Title: J Exp Med 7 Pages: 1523-1527
  • Peer Reviewed
• [Journal Article] Non-self RNA-Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses (2008)
  • Author(s): Takahasi K., Yoneyama M., Nishihori T., Hirai R., Kumeta H., Narita, R., Gale Jr. M., Inagaki F. and Fujita T.
  • Journal Title: Molecular Cell 29 Pages: 428-440
  • Peer Reviewed
• [Journal Article] The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I (2008)
  • Author(s): Cui, S., Eisenacher, K., Kirchhofer, A.,Brzozka, K., Lammens, A., Lammens, K., Fujita, T., Conzelmann, K-K., Krug, A. and Hopfner, K-P.
  • Journal Title: Molecular Cell 29 Pages: 169-179
  • Peer Reviewed
• [Journal Article] Non-self RNA-Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses (2008)
  • Author(s): Takahasi K, Yoneyama M., Nishihori T., Hirai R., Kumeta H., Narita, R., Gale Jr. M., Inagaki F. Fujita T.
  • Journal Title: Molecular Cell 29 Pages: 428-440
  • Peer Reviewed
• [Journal Article] The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I (2008)
  • Author(s): Cui, S., Eisenacher, K., Kirchofer, A., Brzozka, K., Lammens, A., Lammens, K., Fujita, T., Conzelmann, K-K., Krug, A. Hopfner, K-P.
  • Journal Title: Molecular Cell 29 Pages: 169-179
  • Peer Reviewed
• [Journal Article] Non-self RNA-Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses. (2008)
  • Author(s): Takahasi K, Yoneyama M., Nishihori T., Hirai R., Kumeta H., Narita, R., Gale Jr. M., Inagaki F. and Fujita T.:
  • Journal Title: Molecular Cell 29 Pages: 428-440
  • Peer Reviewed
• [Journal Article] The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I. (2008)
  • Author(s): Cui, S., Eisenacher, K., Kirchhofer, A., Brzozka, K., Lammens, A., Lammens, K., Fujita, T., Conzelmann, K-K., Krug, A. and Hopfner, K-P.
  • Journal Title: Molecular Cell 29 Pages: 169-179
  • Peer Reviewed
• [Journal Article] Viral Infections Activate Types I and III Interferon Genes through a Common Mechanism (2007)
  • Author(s): Onoguchi, K., Yoneyama, M., Takemura, A., Akira, S., Taniguchi, T., Namiki, H., and Fujita, T.
  • Journal Title: J. Biol. Chem 282 Pages: 7576-7581
  • Peer Reviewed
• [Journal Article] Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2 (2007)
  • Author(s): Saito, T., Hirai, R., Loo., Yueh-Ming., D, Owen., C, L. Johnson., S., C. Shinha., Akira, S., Fujita T. and Gale Jr., M.
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 582-587
  • Peer Reviewed
• [Journal Article] Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. (2007)
  • Author(s): Saito, T., Hirai, R., Loo., Yueh- Ming., D, Owen., C, L. Johnson., S., C. Shinha., Akira, S., Fujita T. and Gale Jr., M.
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 582-587
  • Peer Reviewed
• [Journal Article] Viral Infections Activate Types I and III Interferon Genes through a Common Mechanism. (2007)
  • Author(s): Onoguchi, K., Yoneyama, M., Takemura, A., Akira, S., Taniguchi, T., Namiki, H., and Fujita, T.
  • Journal Title: J. Biol. Chem, 282 Pages: 7576-7581
  • Peer Reviewed
• [Journal Article] Virus Activates TLR3-Dependent Inflammatory and RIG-I- Dependent Antiviral Responses in Human Lung Epithelial Cells. (2007)
  • Author(s): Le Goffic R, Pothlichet J, Vitour D, Fujita T, Meurs E, Chignard M, Si-Tahar M.
  • Journal Title: J Immunol 178 Pages: 3368-3372
  • Peer Reviewed
• [Journal Article] NS1 Protein of Influenza A Virus Inhibits the Function of Intracytoplasmic Pathogen Sensor, RIG-I. (2007)
  • Author(s): Guo, Z., Chen, L. M., Zeng, H., Gomez, J. A., Plowden, J., Fujita, T., Katz, J. M., Donis, R. O. and Sambhara, S.
  • Journal Title: Am J Respir Cell Mol Biol. 36 Pages: 263-269
  • Peer Reviewed
• [Journal Article] Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125 (2007)
  • Author(s): Arimoto K., Takahashi H., Hishiki T., Konishi H., Fujita T., Shimotohno K.
  • Journal Title: Proc Natl Acad Sci USA. 104 Pages: 7500-7505
  • Peer Reviewed
• [Journal Article] Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response. (2007)
  • Author(s): Tasaka, M., Sakamoto, N., Itakura, Y., Nakagawa, M., Itsui, Y., Sekine-Osajima, Y., Nishimura-Sakurai, Y., Chen, C. H., Yoneyama, M., Fujita, T., Wakita, T., Maekawa, S., Enomoto, N. and Watanabe, M.
  • Journal Title: J. Gen Virol. 88 Pages: 3323-3333
  • Peer Reviewed
• [Journal Article] Triggering antiviral response by RIG-I-related RNA helicases. (2007)
  • Author(s): Fujita, T., Onoguchi, K., Onomoto, K., Hirai, R. and Yoneyama, M.
  • Journal Title: Biochimie 89 Pages: 754-760
  • Peer Reviewed
• [Journal Article] Function of RIG-I-Like receptors in antiviral innate immunity. (2007)
  • Author(s): Yoneyama, M. and Fujita T.
  • Journal Title: Cytokine Growth Factor Rev. 18 Pages: 545-551
• [Journal Article] RIG-I family RNA helicases: Cytoplasmic sensor for antiviral innate immunity. (2007)
  • Author(s): Yoneyama, M. and Fujita, T.
  • Journal Title: J. Biol. Chem. 282 Pages: 15315-15318
• [Journal Article] Cytoplasmic double-stranded DNA sensor. (2007)
  • Author(s): Yoneyama, M. and Fujita, T.
  • Journal Title: Nature Immunology 8 Pages: 907-908
• [Journal Article] Regulation of Antiviral Innate Immune Responses by RIG-I Family of RNA Helicases. (2007)
  • Author(s): Onomoto, K., Yoneyama, M. and Fujita, T.
  • Journal Title: Current Topics in Microbiology and Immunology 316 Pages: 193-205
• [Journal Article] Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2 (2007)
  • Author(s): Saito, T. et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 582-587
• [Journal Article] Viral Infections Activate Types I and III Interferon Genes through a Common Mechanism (2007)
  • Author(s): Onoguchi, K. et al.
  • Journal Title: J. Biol. Chem 282 Pages: 7576-7581
• [Journal Article] Differential role of MDA5 and RIG-I in the recognition of RNA viruses (2006)
  • Author(s): Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., Yamaguchi, O., Otsu, K., Tsujimura, T., Koh, C-S., Reis e Sousa, C., Matsuura, Y., Fujita, T. and Akira, S.
  • Journal Title: Nature 441 Pages: 101-105
  • Peer Reviewed
• [Journal Article] Role of alpha/beta interferon response in the acquisition of poliovirus susceptibility of kidney cells in culture (2006)
  • Author(s): Yoshikawa T., Iwasaki T., Ida-Hosonuma M., Yoneyama M., Fujita T., Horie H., Miyazawa M., Abe S., Simizu B., and Koike S.
  • Journal Title: J. Virology 80 Pages: 4313-4325
  • Peer Reviewed
• [Journal Article] Viral and therapeutic control of IFN-β promoter stimulator 1 during hepatitis C virus infection (2006)
  • Author(s): Loo, Y-M. et al.
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 6001-6006
• [Journal Article] Differential role of MDA5 and RIG-I in the recognition of RNA viruses (2006)
  • Author(s): Kato, H. et al.
  • Journal Title: Nature 441 Pages: 101-105
• [Journal Article] A structural basis for discriminating between self and nonself double-stranded RNAs in mammalian cells (2006)
  • Author(s): Marques J.T. et al.
  • Journal Title: Nature Biotechnology 24 Pages: 559-565
• [Journal Article] NAP1 (NAK-associated protein 1) participates in both the TLR3 and the cytoplasmic pathways in type I interferon (2006)
  • Author(s): Sasai, M. et al.
  • Journal Title: J. Immunology 177 Pages: 8676-8683
• [Presentation] Anti virus and anti cell growth responses induced by non-self RNA sensor, RIG-I RNA helicase. (2008)
  • Author(s): Fujita, T.
  • Organizer: 67th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
  • Year and Date: 2008-10-29
• [Presentation] Mechanism of Foreign RNA Recognition in the Cytoplasm (2008)
  • Author(s): Fujita T.
  • Organizer: 7^<th> Joint Conference of the International Cytokine Society and the International Society for Interferon and Cytokine Research
  • Place of Presentation: Montreal Quebec, Canada
• [Presentation] Non-self RNA Sensing Mechanism of RIG-I-Like Helicase and Activation of Antiviral Immune Responses. XIV (2008)
  • Author(s): Takahasi K, Yoneyama M., Nishihori T., Hirai R., Kumeta H., Narita, R., Gale Jr. M., Inagaki F. and Fujita T.
  • Organizer: International Congress of Virology
  • Place of Presentation: Istanbul, Turkey
• [Presentation] Non-self RNA Sensing Mechanism of RIG-I-Like Helicase and Activation of Antiviral Immune Responses (2008)
  • Author(s): Fujita, T
  • Organizer: Keystone Symposia, Innate Immunity : Signaling Mechanisms
  • Place of Presentation: Keystone, Colorado
• [Presentation] Regulation of interferon gene expression and virus infection of the liver (2008)
  • Author(s): Fujita, T.
  • Organizer: Hepatic Inflammation and Immunity
  • Place of Presentation: Moody Gardens Resort, Galveston, Texas
• [Presentation] Non-self RNA Sensing Mechanism of RIG-I-Like Helicase and Activation of Antiviral Immune Responses. (2008)
  • Author(s): Fujita, T.
  • Organizer: XIV. International Congress of Virology
  • Place of Presentation: Istanbul, Turkey
• [Presentation] Non-self RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. (2008)
  • Author(s): Fujita, T.
  • Organizer: 1st International Centre for Genetic Engineering and Biotechnology Workshop on Human RNA viruses
  • Place of Presentation: Trieste, Italy
• [Presentation] Mechanism of Foreign RNA Recognition in the Cytoplasm. (2008)
  • Author(s): Fujita, T.
  • Organizer: 7th Joint Conference of the International Cytokine Society and the International Society for Interferonand Cytokine Research
  • Place of Presentation: Quebec, Canada
• [Presentation] Non-self RNA Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses (2007)
  • Author(s): Fujita, T.
  • Organizer: 3rd Annual Meeting of the Oligonucleotide Therapeutic Society
  • Place of Presentation: Langenbeck-Virchow Auditorium, Berlin, Germany
  • Year and Date: 2007-10-05
• [Presentation] Non-self RNA Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses. (2007)
  • Author(s): Fujita, T.
  • Organizer: 3rd Annual Meeting of the Oligonucleotide Therapeutic Society
  • Place of Presentation: Langenbeck-Virchow Auditorium, Berlin, Germany
  • Year and Date: 2007-10-05
• [Presentation] 抗ウイルス生体防御のセンサー、RIG-I like receptors (2007)
  • Author(s): 藤田尚志
  • Organizer: 第31回阿蘇シンポジウム
  • Place of Presentation: 阿蘇(阿蘇プリンスホテル)
  • Year and Date: 2007-07-27
• [Presentation] RIG-I family helicases : Cytoplasmic sensor for non-self RNA (2007)
  • Author(s): Fujita, T.
  • Organizer: Viral Immunology Symposium
  • Place of Presentation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD USA
  • Year and Date: 2007-07-23
• [Presentation] RIG-I family helicases: Cytoplasmic sensor for non-self RNA. (2007)
  • Author(s): Fujita, T.
  • Organizer: Viral Immunology Symposium
  • Place of Presentation: 23 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD USA
  • Year and Date: 2007-07-23
• [Presentation] Sensing viruses and antiviral response (2007)
  • Author(s): Fujita, T.
  • Organizer: Gordon Research Conferences : Viruses and Cells
  • Place of Presentation: Tilton School, Tilton NH USA
  • Year and Date: 2007-06-05
• [Presentation] Sensing viruses and antiviral response. (2007)
  • Author(s): Fujita, T.
  • Organizer: Gordon Research Conferences: Viruses and Cells
  • Place of Presentation: Tilton School, Tilton NH USA
  • Year and Date: 2007-06-05
• [Presentation] ウイルスの複製を感知するCARDヘリカーゼ、RIG-Iファミリー (2007)
  • Author(s): 藤田尚志
  • Organizer: 第3回神戸膠原病研究会
  • Place of Presentation: 神戸(ラッセ・ホール)
  • Year and Date: 2007-05-25
• [Presentation] 抗ウイルス自然免疫機構制御するウイルスセンサー、RIG-I like receptor (2007)
  • Author(s): 藤田尚志
  • Organizer: 第13回広島肝臓研究会
  • Place of Presentation: 広島(リーガロイヤルホテル広島)
  • Year and Date: 2007-05-17
• [Presentation] Triggering Antiviral responses and Cell Regulation by the Cytoplasmic RNA Helicase RIG-I (2007)
  • Author(s): Fujita, T.
  • Organizer: Keystone Symposia : Intracellular and Intercellular Signaling in Dendritic Cell Function
  • Place of Presentation: Keystone, CO USA
  • Year and Date: 2007-02-26
• [Presentation] Signal Transduction by Cytoplasmic Virus Receptors (2007)
  • Author(s): Fujita, T.
  • Organizer: Keystone Symposia : Jaks, Stats and Immunity
  • Place of Presentation: Steamboat Springs, CO USA
  • Year and Date: 2007-01-09
• [Presentation] Non-self RNA Sensing Mechanism of RIG-I Helicase and Activation of Antiviral Immune Responses (2007)
  • Author(s): Fujita, T.
  • Organizer: ISICR 2007
  • Place of Presentation: Oxford, UK
• [Presentation] III型インターフェロンはI型インターフェロンと同じ転写制御を受ける (2007)
  • Author(s): 小野口和英、米山光俊、審良静男、谷口維紹、藤田尚志
  • Organizer: 第72回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 京都(京都大学)
• [Presentation] 細胞内ウイルス感染センサーRIG-Iによる非自己RNA認識のメカニズム (2007)
  • Author(s): 米山光俊、平井玲子、成田亮、藤田尚志
  • Organizer: 第72回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 京都(京都大学)
• [Presentation] RIG-I CARDのオリゴマー形成に夜シグナル伝達機構と生理的機能の解析 (2007)
  • Author(s): 尾野本浩司、米山光俊、大島宏之、藤田尚志
  • Organizer: 第72回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 京都(京都大学)
• [Presentation] Triggering Antiviral Responses and host regulation by the Cytoplasmic RNA Helicase RIG-I (2006)
  • Author(s): Fujita, T.
  • Organizer: Cytokines 2006
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2006-08-28
• [Book] 免疫応答と免疫病態の総合的分子理解 : ウイルス感染における細胞内センシング機構 (2008)
  • Author(s): 尾野本浩司, 米山光俊, 藤田尚志
  • Publisher: 南山堂
• [Book] 炎症と免疫 (2007)
  • Author(s): 小野口和英、米山光俊、藤田尚志
  • Publisher: 先端医学社
• [Book] 蛋白質 核酸 酵素 (2007)
  • Author(s): 成田亮、米山光俊、藤田尚志
  • Publisher: 共立出版
• [Book] 免疫応答と免疫病態の総合的分子理解 (2007)
  • Author(s): 尾野本浩司、米山光俊、藤田尚志
  • Publisher: 南山堂
• [Remarks]
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/bunshiiden/index.html