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

2008 Fiscal Year Final Research Report

• 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
• Keywords: 免疫学 / ウイルス / インターフェロン / RNA / ヘリカーゼ

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] 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] 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] 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
• [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
  • Year and Date: 20081012-16
• [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
  • Year and Date: 20080910-15
• [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
  • Year and Date: 20080224-29
• [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
  • Year and Date: 20080125-28
• [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
  • Year and Date: 20070916-19
• [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] 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] 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] 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] 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
• [Remarks]
  • URL: http://www.virus.kyoto-u.ac.jp/Lab/bunshiiden/index.html