RIG-I dependent sensing of poly(dA-dT) via the induction of an RNA polymerase III transcribed RNA intermediate

By A. Ablasser, F. Bauernfeind, G. Hartmann, E. Latz, Katherine A. Fitzgerald, V. Hornung. Nature Immunology, 2009

931 citations recorded by the source corpus.

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-κB. 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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/5c4a3a4b5a23d12f69a701b9d8742be687f0d703

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Citations in the corpus

Immune sensing of DNA (2013, neutral): “Several DDX proteins have been implicated in innate immunity working as RNA sensors (RIG-I and MDA5), signaling molecules (DDX3), and also DNA sensors (Yoneyama et al., 2004; Schröder et al., 2008; Zhang et al., 2011b; Kim et al., 2010).”
STING Specifies IRF3 phosphorylation by TBK1 in the Cytosolic DNA Signaling Pathway (2012, background): “Studies have shown that DNA-dependent RNA polymerase III (Pol III) converts AT-rich DNA, such as poly(dA:dT), into an RNA species that triggers the RIG-I pathway (10, 11).”
Peroxisomes are signaling platforms for antiviral innate immunity (2010, positive): “Defective interfering T (DI-T) particles of VSV were recovered from a cDNA clone of the DI-T genome [24].”
IFI16 is an innate immune sensor for intracellular DNA (2010, background): “RNA polymerase III also responds to transfected poly(dA:dT), which it transcribes into an RNA ligand for RIG-I, leading to DNA-mediated IFN-β induction via the RIG-I pathwa”
Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response (2009, background): “Recent studies have shown that the poly (dA-dT), B-form of dsDNA used in this study, induces RNA polymerase III-dependent innate immune responses both in human cells and in immortalized mouse cells (28, 29).”
Establishing the role of ATP for the function of the RIG-I innate immune sensor (2015, background): “Retinoic acid-inducible gene I (RIG-I) is a cellular innate immune receptor that recognizes viral ribonucleic acid (RNA) in the cytoplasm and consequently initiates a host defense response (Yoneyama et al., 2004; Ablasser et al., 2009; Baum et al., 2010).”
Immune signaling by RIG-I-like receptors (2011, background): “In support of this notion, RIG-I has been reported to signal IFN induction in response to 50ppp AU-RNA polymers that are generated by RNA polymerase III (pol III) transcription with exogenous dAdTDNA as templates (Ablasser et al., 2009; Chiu et al., 2009).”
The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells (2011, background): “RIG-I senses cytosolic DNA (B-form DNA) via RNA polymerase III to trigger responses by transcription factor IRF3–dependent type I interfero”
Quantitative proteomics reveals subset-specific viral recognition in dendritic cells. (2010, background): “, 2009), possibly, at least in the case of EBV, via RNA polymerase III (Ablasser et al., 2009).”
Pattern recognition receptors and inflammation. (2010, background): “Two studies have shown that poly (dA:dT) can be transcribed into dsRNA by polymerase III and that dsRNA is recognized in a RIG-I-IPS-1-dependent manner in human cells or transformed mouse MEFs (Figure 4) (Ablasser et al., 2009; Chiu et al., 2009; Choi et al., 2009).”