Regulation of cellular function by viral RNA sensors

2012 Fiscal Year Final Research Report

• Project Area: Diversity and asymmetry achieved by RNA program
• Project/Area Number: 20112009
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Chiba University (2010-2012); Kyoto University (2008-2009)
• Principal Investigator: YONEYAMA Mitsutoshi 千葉大学, 真菌医学研究センター, 教授 (40260335)
• Research Collaborator: ONOMOTO Koji 千葉大学, 真菌医学研究センター, 助教 (10612202)
• Project Period (FY): 2008 – 2012
• Keywords: ウイルス / シグナル伝達 / RNA

Research Abstract

RIG-1-like receptors(RLRs)are viral RNA sensors, which initiate antiviral innate immunity. In this work, we tried to elucidate molecular machinery underlying RNA recognition by RLRs and physiological significance of RLR-mediated signaling. We revealed 1)accumulation of RLRs in stress granule-like aggregates to trigger antiviral signaling, 2) inhibition of viral infection via induction of specific microRNA, which downregulates viral receptor expression and 3)possible interaction of RIG-I with endogenous self RNA. These observations made substantial progress for understanding of biological function of RLRs.

Research Products

• [Journal Article] Functional characterization of domains of IPS-1 using an inducible oligomerization system (2013)
  • Author(s): Takamatsu S,Onoguchi K, Onomoto K, Narita R, Takahasi K, Ishidate F, Fujiwara TK, Yoneyama M, Kato H, Fujita T
  • Journal Title: PLoS One Volume: 8 Pages: e53578
  • DOI: DOI:10.1371/journal.pone.0053578
  • Peer Reviewed
• [Journal Article] Hepatitis C virus NS4B protein targets STING and abrogates RIG-I-mediated type-I interferon-dependent innate immunity (2013)
  • Author(s): Nitta S, Sakamoto N, Nakagawa M, Kakinuma S, Mishima K, Kusano-kitazume A, Kiyohashi K, Murakawa M, Nishimura-Sakurai Y, Azuma S, Tasaka-Fujita M, asahina Y, Yoneyama M, Fujita T, Watanabe M
  • Journal Title: Hepatology Volume: 57 Pages: 46-58
  • DOI: DOI:10.1002/hep.26017
  • Peer Reviewed
• [Journal Article] Critical Role of an Antiviral Stress Granule Containing RIG-I and PKR in Viral Detection and Innate Immunity (2012)
  • Author(s): Onomoto K, Jogi M, Yoo J-S, Narita R, Morimoto S, Takemura A, Sambhara S, Kawaguchi A, Osari S, Nagata K, Matsumiya T, Namiki H, Yoneyama M, Fujita T
  • Journal Title: PLoS One Volume: 7 Pages: e430331
  • DOI: DOI:10.1371/journal.pone.0043031
  • Peer Reviewed
• [Journal Article] Retinoic Acid-inducible Gene I-inducible miR-23b Inhibits Infections by Minor Group Rhinoviruses through Down-regulation of the Very Low Density Lipoprotein Receptor (2012)
  • Author(s): Ouda R, Onomoto K, Takahasi K, Edwards MR, Kato H, Yoneyama M, Fujita T
  • Journal Title: J Biol Chem Volume: 286 Pages: 26210-26219
  • Peer Reviewed
• [Journal Article] LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses (2010)
  • Author(s): Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 1512-7
  • DOI: DOI:10.1073/pnas.0912986107
  • Peer Reviewed
• [Journal Article] Virus-infection or 5'ppp-RNA activates antiviral signal through redistribution of IPS-1 mediated by MFN1. (2010)
  • Author(s): Onoguchi K, Onomoto K, Takamatsu S, Jogi M, Takemura A, Morimoto S, Julkunen I, Namiki H, Yoneyama M, Fujita T
  • Journal Title: PLoS Pathog Volume: 6 Pages: e1001012
  • DOI: DOI:10.1371/journal.ppat.1001012
  • Peer Reviewed
• [Journal Article] Recognition of viral nucleic acids in innate immunity (2010)
  • Author(s): Yoneyama M, Fujita T
  • Journal Title: Rev Med Virol Volume: 20 Pages: 4-22
  • DOI: DOI:10.1002/rmv.633
  • Peer Reviewed
• [Journal Article] RNA recognition and signal transduction by RIG-I-like receptors (2009)
  • Author(s): Yoneyama M, Fujita T
  • Journal Title: Immunol. Rev Volume: 227 Pages: 54-65
  • DOI: DOI:10.1111/j.1600-065X.2008.00727.x
• [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, Yoneyama M, Fujita T
  • Journal Title: J Biol Chem Volume: 284 Pages: 13348-54
  • DOI: DOI:10.1074/jbc.M809449200
  • Peer Reviewed
• [Journal Article] Structural mechanism of RNA recognition by RIG-I-like receptors (2008)
  • Author(s): Yoneyama M, Fujita T
  • Journal Title: Immunity Volume: 29 Pages: 178-81
  • DOI: DOI:10.1016/j.immuni.2008.07.009
• [Presentation] Analysis of intracellular localization of viral RNA sensor, RLR (2012)
  • Author(s): Onomoto K, Fujita T, Yoneyama M
  • Organizer: The 22^<nd> CDB Meeting "RNA Sciences in Cell and Developmental Biology II
  • Place of Presentation: Kobe
  • Year and Date: 20120611-13
• [Presentation] Stress granule-like aggregates play a critical role in anti-viral innate immunity (2012)
  • Author(s): Yoneyama M
  • Organizer: The 11th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji
  • Year and Date: 2012-09-12
• [Presentation] ウイルス感染に応答した自然免疫誘導の分子機構 (2012)
  • Author(s): 米山光俊
  • Organizer: 第1回千葉大学感染症研究ネットワーク研究会
  • Place of Presentation: 千葉
  • Year and Date: 2012-06-23
• [Presentation] Molecular machinery underlying recognition of non-self viral RNA by RIG-I-like receptors (RLRs) (2011)
  • Author(s): Yoneyama M
  • Organizer: NTU-JST Joint Meeting on RNA & Biofunctions-Asia Studies
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 20111110-12
• [Presentation] Viral non-self RNA is detected by RIG-I-like receptors in cytoplasmic granules (2011)
  • Author(s): Yoneyama M
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] Molecular machinery for detection of viral RNA in innate immune responses (2011)
  • Author(s): Yoneyama M
  • Organizer: Singapore-Japan Joint Forum Emerging Concepts in Microbiology
  • Place of Presentation: Singapore
  • Year and Date: 2011-11-15
• [Presentation] Formation of granule-like structure in detection of viral non-self RNA by RIG-I-like receptor (2011)
  • Author(s): Yoneyama M, Onomoto K, Jogi M, Fujita T
  • Organizer: The 16^<th> Annual Meeting of the RNA Society
  • Place of Presentation: Kyoto
  • Year and Date: 2011-06-18
• [Presentation] Analysis of intracellular localization of viral RNA sensor, RIG-I (2010)
  • Author(s): Onomoto K, Yoneyama M, Fujita T
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe
  • Year and Date: 2010-08-25
• [Presentation] RIG-I ファミリーによるウイルスRNA 認識機構 (2009)
  • Author(s): 米山光俊
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-25
• [Presentation] Non-self RNA sensing mechanism of RIG-I-like receptors (2008)
  • Author(s): Yoneyama M
  • Organizer: The 8^<th> Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji
  • Year and Date: 2008-09-10
• [Remarks]
  • URL: http://www.pf.chiba-u.ac.jp/bunya_kansenmeneki/bunyakansenmeneki/Mol._Immunol.jpn.html