Abstract
Molecular patterns in pathogenic RNAs can be recognized by the innate immune system, and a component of this response is the interferon-induced enzyme RNA-activated protein kinase (PKR). The major activators of PKR have been proposed to be long double-stranded RNAs. We report that RNAs with very limited secondary structures activate PKR in a 5'-triphosphate-dependent fashion in vitro and in vivo. Activation of PKR by 5'-triphosphate RNA is independent of RIG-I and is enhanced by treatment with type 1 interferon (IFN-alpha). Surveillance of molecular features at the 5' end of transcripts by PKR presents a means of allowing pathogenic RNA to be distinguished from self-RNA. The evidence presented here suggests that this form of RNA-based discrimination may be a critical step in mounting an early immune response.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Cell Line, Tumor
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Chlorocebus aethiops
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DEAD Box Protein 58
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DEAD-box RNA Helicases / metabolism
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Enzyme Activation
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Eukaryotic Initiation Factor-2 / metabolism
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Humans
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Immunity, Innate
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Interferon-alpha / immunology
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Interferon-alpha / metabolism
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Interferon-beta / metabolism
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Molecular Sequence Data
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Nucleic Acid Conformation*
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Phosphoric Monoester Hydrolases / metabolism
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Polyphosphates / metabolism
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RNA / chemistry
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RNA / genetics
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RNA / metabolism*
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RNA, Double-Stranded / chemistry
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RNA, Double-Stranded / genetics
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RNA, Double-Stranded / metabolism*
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Receptors, Immunologic
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Transfection
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Vero Cells
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eIF-2 Kinase / metabolism*
Substances
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Eukaryotic Initiation Factor-2
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Interferon-alpha
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Polyphosphates
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RNA, Double-Stranded
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Receptors, Immunologic
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RNA
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Interferon-beta
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eIF-2 Kinase
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Phosphoric Monoester Hydrolases
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RIGI protein, human
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DEAD Box Protein 58
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DEAD-box RNA Helicases
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triphosphoric acid