Abstract
RNA is sensed by Toll-like receptor 7 (TLR7) and TLR8 or by the RNA helicases LGP2, Mda5 and RIG-I to trigger antiviral responses. Much less is known about sensors for DNA. Here we identify a novel DNA-sensing pathway involving RNA polymerase III and RIG-I. In this pathway, AT-rich double-stranded DNA (dsDNA) served as a template for RNA polymerase III and was transcribed into double-stranded RNA (dsRNA) containing a 5'-triphosphate moiety. Activation of RIG-I by this dsRNA induced production of type I interferon and activation of the transcription factor NF-kappaB. This pathway was important in the sensing of Epstein-Barr virus-encoded small RNAs, which were transcribed by RNA polymerase III and then triggered RIG-I activation. Thus, RNA polymerase III and RIG-I are pivotal in sensing viral DNA.
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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DEAD Box Protein 58
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DEAD-box RNA Helicases / immunology*
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DEAD-box RNA Helicases / metabolism
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DNA, Viral / immunology*
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DNA, Viral / metabolism
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Humans
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Interferon Type I / biosynthesis
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism
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Mice
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NF-kappa B / immunology
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NF-kappa B / metabolism
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Poly dA-dT / immunology*
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Poly dA-dT / metabolism
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RNA Polymerase III / immunology*
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RNA Polymerase III / metabolism
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RNA, Double-Stranded / immunology
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RNA, Viral / immunology
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RNA, Viral / metabolism
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Receptors, Immunologic
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription, Genetic
Substances
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DNA, Viral
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Interferon Type I
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NF-kappa B
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RNA, Double-Stranded
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RNA, Viral
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Receptors, Immunologic
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Poly dA-dT
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RNA Polymerase III
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RIGI protein, human
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DEAD Box Protein 58
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DEAD-box RNA Helicases