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PMID:19631370

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Citation

Chiu, YH, Macmillan, JB and Chen, ZJ (2009) RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell 138:576-91

Abstract

Type I interferons (IFNs) are important for antiviral and autoimmune responses. Retinoic acid-induced gene I (RIG-I) and mitochondrial antiviral signaling (MAVS) proteins mediate IFN production in response to cytosolic double-stranded RNA or single-stranded RNA containing 5'-triphosphate (5'-ppp). Cytosolic B form double-stranded DNA, such as poly(dA-dT)*poly(dA-dT) [poly(dA-dT)], can also induce IFN-beta, but the underlying mechanism is unknown. Here, we show that the cytosolic poly(dA-dT) DNA is converted into 5'-ppp RNA to induce IFN-beta through the RIG-I pathway. Biochemical purification led to the identification of DNA-dependent RNA polymerase III (Pol-III) as the enzyme responsible for synthesizing 5'-ppp RNA from the poly(dA-dT) template. Inhibition of RNA Pol-III prevents IFN-beta induction by transfection of DNA or infection with DNA viruses. Furthermore, Pol-III inhibition abrogates IFN-beta induction by the intracellular bacterium Legionella pneumophila and promotes the bacterial growth. These results suggest that RNA Pol-III is a cytosolic DNA sensor involved in innate immune responses.

Links

PubMed PMC2747301 Online version:10.1016/j.cell.2009.06.015

Keywords

Adenosine Triphosphate/metabolism; Animals; Autoimmunity; Cell Line; Cell-Free System; Cytosol/immunology; DNA/immunology; DNA Viruses/immunology; Humans; Immunity, Innate; Interferon-beta/immunology; Interleukin-1beta/immunology; Legionella pneumophila/immunology; Mice; Polyphosphates/metabolism; RNA/chemistry; RNA/immunology; RNA/metabolism; RNA Polymerase III/immunology; RNA Polymerase III/metabolism; RNA, Double-Stranded/metabolism; Signal Transduction; Uridine Triphosphate/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:RPC7

involved_in

GO:0032728: positive regulation of interferon-beta production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RPC7

involved_in

GO:0045089: positive regulation of innate immune response

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RPC4

involved_in

GO:0032728: positive regulation of interferon-beta production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RPC4

involved_in

GO:0045089: positive regulation of innate immune response

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RPC6

involved_in

GO:0032728: positive regulation of interferon-beta production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RPC6

involved_in

GO:0045089: positive regulation of innate immune response

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MAVS

involved_in

GO:0045087: innate immune response

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MAVS

involved_in

GO:0042742: defense response to bacterium

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MAVS

involved_in

GO:0032728: positive regulation of interferon-beta production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DDX58

involved_in

GO:0032728: positive regulation of interferon-beta production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DDX58

involved_in

GO:0045087: innate immune response

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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