DOI: 10.1084/jem.20080091. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid–inducible gene-I and melanoma differentiation

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

10.1084/jem.20080091

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

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.

Bibliography

Kato, H., Takeuchi, O., Mikamo-Satoh, E., Hirai, R., Kawai, T., Matsushita, K., Hiiragi, A., Dermody, T. S., Fujita, T., & Akira, S. (2008). Length-dependent recognition of double-stranded ribonucleic acids by retinoic acidâinducible gene-I and melanoma differentiationâassociated gene 5. The Journal of Experimental Medicine, 205(7), 1601â1610.

Authors 10

Hiroki Kato (first)
Osamu Takeuchi (additional)
Eriko Mikamo-Satoh (additional)
Reiko Hirai (additional)
Tomoji Kawai (additional)
Kazufumi Matsushita (additional)
Akane Hiiragi (additional)
Terence S. Dermody (additional)
Takashi Fujita (additional)
Shizuo Akira (additional)

References 39 Referenced 1,338

10.1016/j.cell.2006.02.015 / Cell. (2006)
10.1038/nri2174 / Nat. Rev. Immunol. (2007)
10.1038/nature06246 / Nature. (2007)
10.1016/j.biochi.2007.01.013 / Biochimie. (2007)
10.1038/35099560 / Nature. (2001)
10.1126/science.1093616 / Science. (2004)
10.1126/science.1093620 / Science. (2004)
10.1038/35047123 / Nature. (2000)
10.1016/S1074-7613(00)80596-8 / Immunity. (1998)
10.1126/science.1087262 / Science. (2003)
10.1146/annurev.immunol.23.021704.115633 / Annu. Rev. Immunol. (2005)
10.1038/ni1087 / Nat. Immunol. (2004)
10.1073/pnas.0407639101 / Proc. Natl. Acad. Sci. USA. (2004)
10.4049/jimmunol.175.8.5260 / J. Immunol. (2005)
10.1038/ni1243 / Nat. Immunol. (2005)
10.1084/jem.20060792 / J. Exp. Med. (2006)
10.1016/j.cell.2005.08.012 / Cell. (2005)
10.1016/j.immuni.2006.04.004 / Immunity. (2006)
10.1038/nature04193 / Nature. (2005)
10.1016/j.molcel.2005.08.014 / Mol. Cell. (2005)
10.1016/S1074-7613(00)00053-4 / Immunity. (2000)
10.1038/nature03464 / Nature. (2005)
10.4049/jimmunol.175.5.2851 / J. Immunol. (2005)
10.1073/pnas.0606699104 / Proc. Natl. Acad. Sci. USA. (2007)
10.4049/jimmunol.178.10.6444 / J. Immunol. (2007)
10.1038/nature04734 / Nature. (2006)
10.1128/JVI.01080-07 / J. Virol. (2008)
10.1073/pnas.0603082103 / Proc. Natl. Acad. Sci. USA. (2006)
10.1126/science.1132505 / Science. (2006)
10.1126/science.1132998 / Science. (2006)
10.1038/nbt1205 / Nat. Biotechnol. (2006)
10.1126/science.122.3176.907 / Science. (1955)
10.1128/JVI.80.10.5059-5064.2006 / J. Virol. (2006)
10.1038/nbt940 / Nat. Biotechnol. (2004)
10.1038/nature06042 / Nature. (2007)
10.1016/S0042-6822(95)80005-0 / Virology. (1995)
10.1016/j.immuni.2005.04.010 / Immunity. (2005)
10.1128/JVI.76.4.1632-1641.2002 / J. Virol. (2002)
10.1016/j.jsb.2005.05.002 / J. Struct. Biol. (2005)

Dates

Type	When
Created	17 years, 1 month ago (July 1, 2008, 7:56 p.m.)
Deposited	2 years ago (July 29, 2023, 11:54 a.m.)
Indexed	1 day, 10 hours ago (Aug. 26, 2025, 3:14 a.m.)
Issued	17 years, 1 month ago (June 30, 2008)
Published	17 years, 1 month ago (June 30, 2008)
Published Online	17 years, 1 month ago (June 30, 2008)
Published Print	17 years, 1 month ago (July 7, 2008)

Funders 0

None

BibTeX

@article{Kato_2008, title={Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid–inducible gene-I and melanoma differentiation–associated gene 5}, volume={205}, ISSN={0022-1007}, url={http://dx.doi.org/10.1084/jem.20080091}, DOI={10.1084/jem.20080091}, number={7}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Kato, Hiroki and Takeuchi, Osamu and Mikamo-Satoh, Eriko and Hirai, Reiko and Kawai, Tomoji and Matsushita, Kazufumi and Hiiragi, Akane and Dermody, Terence S. and Fujita, Takashi and Akira, Shizuo}, year={2008}, month=jun, pages={1601–1610} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        26
      ]
    ],
    "date-time": "2025-08-26T07:14:07Z",
    "timestamp": 1756192447575
  },
  "reference-count": 39,
  "publisher": "Rockefeller University Press",
  "issue": "7",
  "content-domain": {
    "domain": [
      "rupress.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2008,
        7,
        7
      ]
    ]
  },
  "abstract": "<jats:p>The ribonucleic acid (RNA) helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation\u2013associated gene 5 (MDA5) recognize distinct viral and synthetic RNAs, leading to the production of interferons. Although 5\u2032-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\u2013mediated recognition. Collectively, RIG-I detects dsRNAs without a 5\u2032-triphosphate end, and RIG-I and MDA5 selectively recognize short and long dsRNAs, respectively.</jats:p>",
  "DOI": "10.1084/jem.20080091",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2008,
        7,
        1
      ]
    ],
    "date-time": "2008-07-01T23:56:29Z",
    "timestamp": 1214956589000
  },
  "page": "1601-1610",
  "update-policy": "http://dx.doi.org/10.1084/jem.crossmarkpolicy",
  "source": "Crossref",
  "is-referenced-by-count": 1338,
  "title": "Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid\u2013inducible gene-I and melanoma differentiation\u2013associated gene 5",
  "prefix": "10.1084",
  "volume": "205",
  "author": [
    {
      "given": "Hiroki",
      "family": "Kato",
      "sequence": "first",
      "affiliation": [
        {
          "name": "1Laboratory of Host Defense, World Premiere International Immunology Frontier Research Center,"
        },
        {
          "name": "2Research Institute for Microbial Diseases,"
        }
      ]
    },
    {
      "given": "Osamu",
      "family": "Takeuchi",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "1Laboratory of Host Defense, World Premiere International Immunology Frontier Research Center,"
        },
        {
          "name": "2Research Institute for Microbial Diseases,"
        }
      ]
    },
    {
      "given": "Eriko",
      "family": "Mikamo-Satoh",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "3Institute for Scientific and Industrial Research, Osaka University, Suita, Osaka 565-0871, Japan"
        },
        {
          "name": "4Department of Pharmacy, Hyogo University of Health Sciences, Cyuo-ku, Kobe, Hyogo 650-8530, Japan"
        }
      ]
    },
    {
      "given": "Reiko",
      "family": "Hirai",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "5Laboratory of Molecular Genetics, Institute for Virus Research, and"
        }
      ]
    },
    {
      "given": "Tomoji",
      "family": "Kawai",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "3Institute for Scientific and Industrial Research, Osaka University, Suita, Osaka 565-0871, Japan"
        }
      ]
    },
    {
      "given": "Kazufumi",
      "family": "Matsushita",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "1Laboratory of Host Defense, World Premiere International Immunology Frontier Research Center,"
        },
        {
          "name": "2Research Institute for Microbial Diseases,"
        }
      ]
    },
    {
      "given": "Akane",
      "family": "Hiiragi",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "6Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan"
        }
      ]
    },
    {
      "given": "Terence S.",
      "family": "Dermody",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "7Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232"
        }
      ]
    },
    {
      "given": "Takashi",
      "family": "Fujita",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "5Laboratory of Molecular Genetics, Institute for Virus Research, and"
        },
        {
          "name": "6Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan"
        }
      ]
    },
    {
      "given": "Shizuo",
      "family": "Akira",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "1Laboratory of Host Defense, World Premiere International Immunology Frontier Research Center,"
        },
        {
          "name": "2Research Institute for Microbial Diseases,"
        }
      ]
    }
  ],
  "member": "291",
  "published-online": {
    "date-parts": [
      [
        2008,
        6,
        30
      ]
    ]
  },
  "reference": [
    {
      "key": "2023072915540213800_BIB1",
      "doi-asserted-by": "crossref",
      "first-page": "783",
      "DOI": "10.1016/j.cell.2006.02.015",
      "volume": "124",
      "year": "2006",
      "journal-title": "Cell."
    },
    {
      "key": "2023072915540213800_BIB2",
      "doi-asserted-by": "crossref",
      "first-page": "753",
      "DOI": "10.1038/nri2174",
      "volume": "7",
      "year": "2007",
      "journal-title": "Nat. Rev. Immunol."
    },
    {
      "key": "2023072915540213800_BIB3",
      "doi-asserted-by": "crossref",
      "first-page": "819",
      "DOI": "10.1038/nature06246",
      "volume": "449",
      "year": "2007",
      "journal-title": "Nature."
    },
    {
      "key": "2023072915540213800_BIB4",
      "doi-asserted-by": "crossref",
      "first-page": "754",
      "DOI": "10.1016/j.biochi.2007.01.013",
      "volume": "89",
      "year": "2007",
      "journal-title": "Biochimie."
    },
    {
      "key": "2023072915540213800_BIB5",
      "doi-asserted-by": "crossref",
      "first-page": "732",
      "DOI": "10.1038/35099560",
      "volume": "413",
      "year": "2001",
      "journal-title": "Nature."
    },
    {
      "key": "2023072915540213800_BIB6",
      "doi-asserted-by": "crossref",
      "first-page": "1529",
      "DOI": "10.1126/science.1093616",
      "volume": "303",
      "year": "2004",
      "journal-title": "Science."
    },
    {
      "key": "2023072915540213800_BIB7",
      "doi-asserted-by": "crossref",
      "first-page": "1526",
      "DOI": "10.1126/science.1093620",
      "volume": "303",
      "year": "2004",
      "journal-title": "Science."
    },
    {
      "key": "2023072915540213800_BIB8",
      "doi-asserted-by": "crossref",
      "first-page": "740",
      "DOI": "10.1038/35047123",
      "volume": "408",
      "year": "2000",
      "journal-title": "Nature."
    },
    {
      "key": "2023072915540213800_BIB9",
      "doi-asserted-by": "crossref",
      "first-page": "143",
      "DOI": "10.1016/S1074-7613(00)80596-8",
      "volume": "9",
      "year": "1998",
      "journal-title": "Immunity."
    },
    {
      "key": "2023072915540213800_BIB10",
      "doi-asserted-by": "crossref",
      "first-page": "640",
      "DOI": "10.1126/science.1087262",
      "volume": "301",
      "year": "2003",
      "journal-title": "Science."
    },
    {
      "key": "2023072915540213800_BIB11",
      "doi-asserted-by": "crossref",
      "first-page": "275",
      "DOI": "10.1146/annurev.immunol.23.021704.115633",
      "volume": "23",
      "year": "2005",
      "journal-title": "Annu. Rev. Immunol."
    },
    {
      "key": "2023072915540213800_BIB12",
      "doi-asserted-by": "crossref",
      "first-page": "730",
      "DOI": "10.1038/ni1087",
      "volume": "5",
      "year": "2004",
      "journal-title": "Nat. Immunol."
    },
    {
      "key": "2023072915540213800_BIB13",
      "doi-asserted-by": "crossref",
      "first-page": "17264",
      "DOI": "10.1073/pnas.0407639101",
      "volume": "101",
      "year": "2004",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072915540213800_BIB14",
      "doi-asserted-by": "crossref",
      "first-page": "5260",
      "DOI": "10.4049/jimmunol.175.8.5260",
      "volume": "175",
      "year": "2005",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072915540213800_BIB15",
      "doi-asserted-by": "crossref",
      "first-page": "981",
      "DOI": "10.1038/ni1243",
      "volume": "6",
      "year": "2005",
      "journal-title": "Nat. Immunol."
    },
    {
      "key": "2023072915540213800_BIB16",
      "doi-asserted-by": "crossref",
      "first-page": "1795",
      "DOI": "10.1084/jem.20060792",
      "volume": "203",
      "year": "2006",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072915540213800_BIB17",
      "doi-asserted-by": "crossref",
      "first-page": "669",
      "DOI": "10.1016/j.cell.2005.08.012",
      "volume": "122",
      "year": "2005",
      "journal-title": "Cell."
    },
    {
      "key": "2023072915540213800_BIB18",
      "doi-asserted-by": "crossref",
      "first-page": "633",
      "DOI": "10.1016/j.immuni.2006.04.004",
      "volume": "24",
      "year": "2006",
      "journal-title": "Immunity."
    },
    {
      "key": "2023072915540213800_BIB19",
      "doi-asserted-by": "crossref",
      "first-page": "1167",
      "DOI": "10.1038/nature04193",
      "volume": "437",
      "year": "2005",
      "journal-title": "Nature."
    },
    {
      "key": "2023072915540213800_BIB20",
      "doi-asserted-by": "crossref",
      "first-page": "727",
      "DOI": "10.1016/j.molcel.2005.08.014",
      "volume": "19",
      "year": "2005",
      "journal-title": "Mol. Cell."
    },
    {
      "key": "2023072915540213800_BIB21",
      "doi-asserted-by": "crossref",
      "first-page": "539",
      "DOI": "10.1016/S1074-7613(00)00053-4",
      "volume": "13",
      "year": "2000",
      "journal-title": "Immunity."
    },
    {
      "key": "2023072915540213800_BIB22",
      "doi-asserted-by": "crossref",
      "first-page": "772",
      "DOI": "10.1038/nature03464",
      "volume": "434",
      "year": "2005",
      "journal-title": "Nature."
    },
    {
      "key": "2023072915540213800_BIB23",
      "doi-asserted-by": "crossref",
      "first-page": "2851",
      "DOI": "10.4049/jimmunol.175.5.2851",
      "volume": "175",
      "year": "2005",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072915540213800_BIB24",
      "doi-asserted-by": "crossref",
      "first-page": "582",
      "DOI": "10.1073/pnas.0606699104",
      "volume": "104",
      "year": "2007",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072915540213800_BIB25",
      "doi-asserted-by": "crossref",
      "first-page": "6444",
      "DOI": "10.4049/jimmunol.178.10.6444",
      "volume": "178",
      "year": "2007",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072915540213800_BIB26",
      "doi-asserted-by": "crossref",
      "first-page": "101",
      "DOI": "10.1038/nature04734",
      "volume": "441",
      "year": "2006",
      "journal-title": "Nature."
    },
    {
      "key": "2023072915540213800_BIB27",
      "doi-asserted-by": "crossref",
      "first-page": "335",
      "DOI": "10.1128/JVI.01080-07",
      "volume": "82",
      "year": "2008",
      "journal-title": "J. Virol."
    },
    {
      "key": "2023072915540213800_BIB28",
      "doi-asserted-by": "crossref",
      "first-page": "8459",
      "DOI": "10.1073/pnas.0603082103",
      "volume": "103",
      "year": "2006",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072915540213800_BIB29",
      "doi-asserted-by": "crossref",
      "first-page": "994",
      "DOI": "10.1126/science.1132505",
      "volume": "314",
      "year": "2006",
      "journal-title": "Science."
    },
    {
      "key": "2023072915540213800_BIB30",
      "doi-asserted-by": "crossref",
      "first-page": "997",
      "DOI": "10.1126/science.1132998",
      "volume": "314",
      "year": "2006",
      "journal-title": "Science."
    },
    {
      "key": "2023072915540213800_BIB31",
      "doi-asserted-by": "crossref",
      "first-page": "559",
      "DOI": "10.1038/nbt1205",
      "volume": "24",
      "year": "2006",
      "journal-title": "Nat. Biotechnol."
    },
    {
      "key": "2023072915540213800_BIB32",
      "doi-asserted-by": "crossref",
      "first-page": "907",
      "DOI": "10.1126/science.122.3176.907",
      "volume": "122",
      "year": "1955",
      "journal-title": "Science."
    },
    {
      "key": "2023072915540213800_BIB33",
      "doi-asserted-by": "crossref",
      "first-page": "5059",
      "DOI": "10.1128/JVI.80.10.5059-5064.2006",
      "volume": "80",
      "year": "2006",
      "journal-title": "J. Virol."
    },
    {
      "key": "2023072915540213800_BIB34",
      "doi-asserted-by": "crossref",
      "first-page": "321",
      "DOI": "10.1038/nbt940",
      "volume": "22",
      "year": "2004",
      "journal-title": "Nat. Biotechnol."
    },
    {
      "key": "2023072915540213800_BIB35",
      "doi-asserted-by": "crossref",
      "first-page": "816",
      "DOI": "10.1038/nature06042",
      "volume": "448",
      "year": "2007",
      "journal-title": "Nature."
    },
    {
      "key": "2023072915540213800_BIB36",
      "doi-asserted-by": "crossref",
      "first-page": "760",
      "DOI": "10.1016/S0042-6822(95)80005-0",
      "volume": "206",
      "year": "1995",
      "journal-title": "Virology."
    },
    {
      "key": "2023072915540213800_BIB37",
      "doi-asserted-by": "crossref",
      "first-page": "19",
      "DOI": "10.1016/j.immuni.2005.04.010",
      "volume": "23",
      "year": "2005",
      "journal-title": "Immunity."
    },
    {
      "key": "2023072915540213800_BIB38",
      "doi-asserted-by": "crossref",
      "first-page": "1632",
      "DOI": "10.1128/JVI.76.4.1632-1641.2002",
      "volume": "76",
      "year": "2002",
      "journal-title": "J. Virol."
    },
    {
      "key": "2023072915540213800_BIB39",
      "doi-asserted-by": "crossref",
      "first-page": "106",
      "DOI": "10.1016/j.jsb.2005.05.002",
      "volume": "151",
      "year": "2005",
      "journal-title": "J. Struct. Biol."
    }
  ],
  "container-title": "The Journal of Experimental Medicine",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://rupress.org/jem/article-pdf/205/7/1601/1899217/jem_20080091.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://rupress.org/jem/article-pdf/205/7/1601/1899217/jem_20080091.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        7,
        29
      ]
    ],
    "date-time": "2023-07-29T15:54:36Z",
    "timestamp": 1690646076000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://rupress.org/jem/article/205/7/1601/46724/Length-dependent-recognition-of-double-stranded"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2008,
        6,
        30
      ]
    ]
  },
  "references-count": 39,
  "journal-issue": {
    "issue": "7",
    "published-print": {
      "date-parts": [
        [
          2008,
          7,
          7
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1084/jem.20080091",
  "relation": {
    "has-review": [
      {
        "id-type": "doi",
        "id": "10.3410/f.1116502.572529",
        "asserted-by": "object"
      }
    ]
  },
  "ISSN": [
    "1540-9538",
    "0022-1007"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2008,
        6,
        30
      ]
    ]
  }
}