Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5.
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.
Kato
Hiroki
H
Laboratory of Host Defense, World Premiere International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Takeuchi
Osamu
O
Mikamo-Satoh
Eriko
E
Hirai
Reiko
R
Kawai
Tomoji
T
Matsushita
Kazufumi
K
Hiiragi
Akane
A
Dermody
Terence S
TS
Fujita
Takashi
T
Akira
Shizuo
S
D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D000072640:Interferon-Induced Helicase, IFIH1; D051379:Mice; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D054243:Vesicular Stomatitis / Q000235:genetics / Q000378:metabolism*; D018116:Vesiculovirus / Q000235:genetics / Q000378:metabolism*
D012330:RNA, Double-Stranded; D012367:RNA, Viral; C503356:Ddx58 protein, mouse; C510592:Ifih1 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1