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
Comment
. 2016 Apr 15;35(8):796-7.
doi: 10.15252/embj.201694226. Epub 2016 Mar 23.

cGAS-STING do it again: pivotal role in RNase H2 genetic disease

Matteo Gentili  1 , Nicolas Manel  1
Affiliations
Comment

cGAS-STING do it again: pivotal role in RNase H2 genetic disease

Matteo Gentili et al. EMBO J. .

Abstract

RNase H2 is a susceptibility gene for the Aicardi–Goutières syndrome (AGS), a genetic auto‐inflammatory disease. Mackenzie and colleagues now report a tractable mouse model for the disease, implicating the cGAS‐STING pathway.

PubMed Disclaimer

Figures

Figure 1
Figure 1. AGS mutation in RNase H2 activates the cGAS‐STING pathway
Top: RNA:DNA hybrids are produced during transcription and DNA replication. RNase H2, composed of 3 subunits A, B, and C, excises ribonucleotides, leading to DNA repair. Bottom: When RNase H2 carries a mutation found in patients with Aicardi–Goutières syndrome (AGS), RNA:DNA hybrids are not processed properly and lead to the activation of the nucleic acid sensor cGAS. cGAS produces the dinucleotide cyclic GMP‐AMP (cGAMP), which activates STING, leading to the expression of type I IFN‐stimulated genes and inflammation, as observed in AGS.
See this image and copyright information in PMC

Comment on

  • Ribonuclease H2 mutations induce a cGAS/STING-dependent innate immune response.
    Mackenzie KJ, Carroll P, Lettice L, Tarnauskaitė Ž, Reddy K, Dix F, Revuelta A, Abbondati E, Rigby RE, Rabe B, Kilanowski F, Grimes G, Fluteau A, Devenney PS, Hill RE, Reijns MA, Jackson AP. Mackenzie KJ, et al. EMBO J. 2016 Apr 15;35(8):831-44. doi: 10.15252/embj.201593339. Epub 2016 Feb 22. EMBO J. 2016. PMID: 26903602 Free PMC article.

References

    1. Crow YJ, Manel N (2015) Aicardi‐Goutieres syndrome and the type I interferonopathies. Nat Rev Immunol 15: 429–440 - PubMed
    1. Hasan M, Fermaintt CS, Gao N, Sakai T, Miyazaki T, Jiang S, Li QZ, Atkinson JP, Morse HC 3rd, Lehrman MA, Yan N (2015) Cytosolic nuclease TREX1 regulates oligosaccharyltransferase activity independent of nuclease activity to suppress immune activation. Immunity 43: 463–474 - PMC - PubMed
    1. Mackenzie KJ, Carroll P, Lettice L, Tarnauskaite Z, Reddy K, Dix F, Revuelta A, Abbondati E, Rigby RE, Rabe B, Kilanowski F, Grimes G, Fluteau A, Devenney PS, Hill RE, Reijns MA, Jackson AP (2016) Ribonuclease H2 mutations induce a cGAS/STING‐dependent innate immune response. EMBO J 35: 831–844 - PMC - PubMed
    1. Manel N, Hogstad B, Wang Y, Levy DE, Unutmaz D, Littman DR (2010) A cryptic sensor for HIV‐1 activates antiviral innate immunity in dendritic cells. Nature 467: 214–217 - PMC - PubMed
    1. McGonagle D, McDermott MF (2006) A proposed classification of the immunological diseases. PLoS Med 3: e297 - PMC - PubMed

Publication types

MeSH terms

Supplementary concepts