Abstract
The protein kinase regulated by RNA (PKR) and the adenosine deaminase acting on RNA (ADAR1) are interferon-inducible enzymes that play important roles in biologic processes including the antiviral actions of interferons, signal transduction, and apoptosis. PKR catalyzes the RNA-dependent phosphorylation of protein synthesis initiation factor eIF-2 alpha, thereby leading to altered translational patterns in interferon-treated and virus-infected cells. PKR also modulates signal transduction responses, including the induction of interferon. ADAR1 catalyzes the deamination of adenosine (A) to generate inosine (I) in RNAs with double-stranded character. Because I is recognized as G instead of A, A-to-I editing by ADAR1 can lead to genetic recoding and altered RNA structures. The importance of PKR and ADAR1 in innate antiviral immunity is illustrated by a number of viruses that encode either RNA or protein viral gene products that antagonize PKR and ADAR1 enzymatic activity, localization, or stability.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Adenosine Deaminase / genetics
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Adenosine Deaminase / immunology
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Adenosine Deaminase / metabolism*
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Animals
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Antiviral Agents / immunology
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Antiviral Agents / metabolism
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Apoptosis
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Enzyme Inhibitors / immunology
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Enzyme Inhibitors / metabolism
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Eukaryotic Initiation Factor-2 / genetics
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Eukaryotic Initiation Factor-2 / immunology
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Eukaryotic Initiation Factor-2 / metabolism
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Humans
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Immunity, Innate
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Interferons / immunology
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RNA Editing
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RNA Virus Infections / enzymology*
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RNA Virus Infections / genetics*
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RNA Virus Infections / immunology
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RNA Viruses / pathogenicity
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RNA Viruses / physiology*
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RNA-Binding Proteins
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Signal Transduction
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Viral Proteins / immunology
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Viral Proteins / metabolism
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eIF-2 Kinase / genetics
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eIF-2 Kinase / immunology
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eIF-2 Kinase / metabolism*
Substances
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Antiviral Agents
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Enzyme Inhibitors
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Eukaryotic Initiation Factor-2
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RNA-Binding Proteins
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Viral Proteins
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Interferons
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eIF-2 Kinase
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ADARB1 protein, human
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Adenosine Deaminase