Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Jan;91(1):78-85.
doi: 10.1016/j.ejcb.2011.01.015. Epub 2011 Apr 14.

Sensing of viral nucleic acids by RIG-I: from translocation to translation

Andreas Schmidt  1 , Simon Rothenfusser, Karl-Peter Hopfner
Affiliations
Review

Sensing of viral nucleic acids by RIG-I: from translocation to translation

Andreas Schmidt et al. Eur J Cell Biol. 2012 Jan.

Abstract

The innate immune system is a first layer of defense against infection by pathogens. It responds to pathogens by activating host defense mechanisms via interferon and inflammatory cytokine expression. Pathogen associated molecular patterns (PAMPs) are sensed by specific pattern recognition receptors. Among those, the ATP dependent helicase related RIG-I like receptors RIG-I, MDA5 and LGP2 sense the presence of viral RNA in the cytoplasm of host cells. While the precise PAMPs and functions of MDA5 or LGP2 are still unclear, RIG-I senses predominantly viral RNA containing a 5'-triphosphate along with dsRNA regions. Here we review our current knowledge of how these PAMPs are sensed and integrated by RIG-I, and how RIG-I's innate immune function can be used in translational medical approaches.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Domain structure of and signalling by the RLR family members
(A) RIG-I, MDA5 and LGP2 share a C-terminal RD domain and an SF2-type ATPase domain. In addition RIG-I and MDA5 have two N-termial CARD domains required for signalling via IPS1 that are absent in LGP2. (B) Signalling in the RLR pathway is initiated by binding of RNA to the respective receptor (RIG-I or MDA5). LGP2 may assist ligand recognition or inhibit signalling under certain circumstances. Binding of one of the receptor proteins to the mitochondrial adapter IPS1 leads to the activation of transcription factors of the IRF and NF-kB families. This ultimately leads to the production of interferons and inflammatory cytokines.
Figure 2
Figure 2. PAMPs recognised by RIG-I are found in viral genomic RNAs
Recent studies suggest that DI-genomic RNA may serve as a principal ligand for RIG-I in the situation of viral infection of a cell. In the case of Sendai Virus DI-genomes arise by copy back mechanisms forming a self-complementary structure (left). Influenza virus genome segments are inherently self-complementary at the ends (panhandle) but may also give rise to internally deleted DI-genomic segments (right).
Figure 3
Figure 3. Structures and mechanisms of RLR activation
(A) Regulatory/Repressor domains (ribbon models with highlighted secondary structure) of RIG-I, MDA5 and LGP2 possess the same fold, including a zinc (magenta sphere) binding site. Nucleic acids bind to a central core RNA binding site, while specificity for different types of RNA ends is provided by a specificity loop. (B) RDs emerge as dsRNA end binding domains. RIG-I RD preferentially binds to dsRNA ends containing a triphosphate moiety (color coded spheres) while LGP2 appears to recognise unphosphorylated ends. (C) Possible model for PAMP integration and signalling by RIG-I. Binding of pppRNA to RD and the SF2 domain could switch the enzyme into an active dimer. Translocation of the SF2 domain on dsRNA may induce a conformational change in RIG-I with exposed CARDs, leading to ubiquitylation and interaction with the IPS1 adaptor.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ablasser A, Bauernfeind F, Hartmann G, Latz E, Fitzgerald KA, Hornung V. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol. 2009;10:1065–1072. - PMC - PubMed
    1. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801. - PubMed
    1. Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S, Randall RE. The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc Natl Acad Sci U S A. 2004;101:17264–17269. - PMC - PubMed
    1. Bamming D, Horvath CM. Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I and LGP2. J Biol Chem. 2009;284:9700–9712. - PMC - PubMed
    1. Baril M, Racine ME, Penin F, Lamarre D. MAVS dimer is a crucial signaling component of innate immunity and the target of hepatitis C virus NS3/4A protease. J Virol. 2009;83:1299–1311. - PMC - PubMed

Publication types

MeSH terms