RNA Polymerase III Detects Cytosolic DNA and Induces Type I Interferons through the RIG-I Pathway

Research output: Contribution to journalArticle

659 Citations (Scopus)

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-β, 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-β 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-β induction by transfection of DNA or infection with DNA viruses. Furthermore, Pol-III inhibition abrogates IFN-β 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.

Original languageEnglish (US)
Pages (from-to)576-591
Number of pages16
JournalCell
Volume138
Issue number3
DOIs
StatePublished - Aug 7 2009

Fingerprint

RNA Polymerase III
Interferon Type I
Tretinoin
Interferons
Poly dA-dT
Genes
DNA
RNA
Antiviral Agents
DNA Virus Infections
Legionella pneumophila
Mitochondrial Genes
Double-Stranded RNA
Autoimmunity
Viruses
Innate Immunity
Purification
Transfection
Bacteria
Sensors

Keywords

  • MOLIMMUNO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

RNA Polymerase III Detects Cytosolic DNA and Induces Type I Interferons through the RIG-I Pathway. / Chiu, Yu Hsin; MacMillan, John B.; Chen, Zhijian J.

In: Cell, Vol. 138, No. 3, 07.08.2009, p. 576-591.

Research output: Contribution to journalArticle

@article{5d125c73b1214a8c9856c2ca09449c75,
title = "RNA Polymerase III Detects Cytosolic DNA and Induces Type I Interferons through the RIG-I Pathway",
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-β, 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-β 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-β induction by transfection of DNA or infection with DNA viruses. Furthermore, Pol-III inhibition abrogates IFN-β 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.",
keywords = "MOLIMMUNO",
author = "Chiu, {Yu Hsin} and MacMillan, {John B.} and Chen, {Zhijian J.}",
year = "2009",
month = "8",
day = "7",
doi = "10.1016/j.cell.2009.06.015",
language = "English (US)",
volume = "138",
pages = "576--591",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - RNA Polymerase III Detects Cytosolic DNA and Induces Type I Interferons through the RIG-I Pathway

AU - Chiu, Yu Hsin

AU - MacMillan, John B.

AU - Chen, Zhijian J.

PY - 2009/8/7

Y1 - 2009/8/7

N2 - 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-β, 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-β 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-β induction by transfection of DNA or infection with DNA viruses. Furthermore, Pol-III inhibition abrogates IFN-β 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.

AB - 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-β, 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-β 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-β induction by transfection of DNA or infection with DNA viruses. Furthermore, Pol-III inhibition abrogates IFN-β 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.

KW - MOLIMMUNO

UR - http://www.scopus.com/inward/record.url?scp=68049092912&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68049092912&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2009.06.015

DO - 10.1016/j.cell.2009.06.015

M3 - Article

VL - 138

SP - 576

EP - 591

JO - Cell

JF - Cell

SN - 0092-8674

IS - 3

ER -