The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Cytosolic RNA:DNA hybrids activate the cGAS –STING axis
Open accessAbstract
Intracellular recognition of non‐self and also self‐nucleic acids can result in the initiation of potent pro‐inflammatory and antiviral cytokine responses. Most recently, cGAS was shown to be critical for the recognition of cytoplasmic dsDNA. Binding of dsDNA to cGAS results in the synthesis of cGAMP (2′–5′), which then binds to the endoplasmic reticulum resident protein STING. This initiates a signaling cascade that triggers the induction of an antiviral immune response. While most studies on intracellular nucleic acids have focused on dsRNA or dsDNA, it has remained unexplored whether cytosolic RNA:DNA hybrids are also sensed by the innate immune system. Studying synthetic RNA:DNA hybrids, we indeed observed a strong type I interferon response upon cytosolic delivery of this class of molecule. Studies in THP‐1 knockout cells revealed that the recognition of RNA:DNA hybrids is completely attributable to the cGAS –STING pathway. Moreover, in vitro studies showed that recombinant cGAS produced cGAMP upon RNA:DNA hybrid recognition. Altogether, our results introduce RNA:DNA hybrids as a novel class of intracellular PAMP molecules and describe an alternative cGAS ligand next to dsDNA.
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Cites
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The HADDOCK web server for data-driven biomolecular docking
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Cited by
Molecular mechanisms and cellular functions of cGAS–STING signalling
Hopfner, K.-P., & Hornung, V. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0244-x · Cited by 2,052
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DNA sensing by the cGAS–STING pathway in health and disease
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The Cytosolic DNA-Sensing cGAS–STING Pathway in Cancer
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STING: infection, inflammation and cancer.
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Metadata
- Authors
- Mankan, A. K., Schmidt, T., Chauhan, D., Goldeck, M., Höning, K., Gaidt, M., Kubarenko, A. V., Andreeva, L., Hopfner, K., & Hornung, V.
- Venue
- The EMBO Journal
- Published
- 2014-11-25
- Volume
- 33
- Issue
- 24
- Pages
- 2937-2946
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- OpenAlex
- W2168252967
- Cited by
- 359
- References
- 35
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- bronze
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