The Journal of Experimental Medicine
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Published online June 30, 2008
doi:10.1084/jem.20080091
The Journal of Experimental Medicine, Vol. 205, No. 7, 1601-1610
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Kato et al.
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ARTICLE

 Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid–inducible gene-I and melanoma differentiation–associated gene 5

Hiroki Kato1,2, Osamu Takeuchi1,2, Eriko Mikamo-Satoh3,4, Reiko Hirai5, Tomoji Kawai3, Kazufumi Matsushita1,2, Akane Hiiragi6, Terence S. Dermody7, Takashi Fujita5,6, and Shizuo Akira1,2

1 Laboratory of Host Defense, World Premiere International Immunology Frontier Research Center, 2 Research Institute for Microbial Diseases, 3 Institute for Scientific and Industrial Research, Osaka University, Suita, Osaka 565-0871, Japan
4 Department of Pharmacy, Hyogo University of Health Sciences, Cyuo-ku, Kobe, Hyogo 650-8530, Japan
5 Laboratory of Molecular Genetics, Institute for Virus Research, and 6 Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan
7 Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232

CORRESPONDENCE Shizuo Akira:sakira{at}biken.osaka-u.ac.jp

The ribonucleic acid (RNA) helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation–associated gene 5 (MDA5) recognize distinct viral and synthetic RNAs, leading to the production of interferons. Although 5'-triphosphate single-stranded RNA is a RIG-I ligand, the role of RIG-I and MDA5 in double-stranded (ds) RNA recognition remains to be characterized. In this study, we show that the length of dsRNA is important for differential recognition by RIG-I and MDA5. The MDA5 ligand, polyinosinic-polycytidylic acid, was converted to a RIG-I ligand after shortening of the dsRNA length. In addition, viral dsRNAs differentially activated RIG-I and MDA5, depending on their length. Vesicular stomatitis virus infection generated dsRNA, which is responsible for RIG-I–mediated recognition. Collectively, RIG-I detects dsRNAs without a 5'-triphosphate end, and RIG-I and MDA5 selectively recognize short and long dsRNAs, respectively.

Abbreviations used in this paper: AFM, atomic force microscope; CARD, caspase-recruitment domain; cDC, conventional DC; CIAP, calf intestine alkaline phosphatase; DI, defective interfering; dsRNA, double-stranded RNA; EMCV, encephalomyocarditis virus; IPS-1, IFN-β stimulator-1; MEF, mouse embryonic fibroblast; MDA5, melanoma differentiation–associated gene 5; pDC, plasmacytoid DC; PNPase, polynucleotide phosphorylase; poly I:C, polyinosine-polycytidylic acid; PRR, pattern recognition receptor; RIG-I, retinoic acid-inducible gene-I; RLH, RIG-I–like helicase; ssRNA, single-stranded RNA; TIR, Toll/IL-1 receptor homology; TLR, Toll-like receptor; VSV, vesicular stomatitis virus.


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