Title |
Cytosolic RNA:DNA hybrids activate the cGAS–STING axis
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Published in |
EMBO Journal, November 2014
|
DOI | 10.15252/embj.201488726 |
Pubmed ID | |
Authors |
Arun K Mankan, Tobias Schmidt, Dhruv Chauhan, Marion Goldeck, Klara Höning, Moritz Gaidt, Andrew V Kubarenko, Liudmila Andreeva, Karl-Peter Hopfner, Veit Hornung |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 3 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 67% |
Scientists | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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France | 2 | <1% |
Germany | 1 | <1% |
United Kingdom | 1 | <1% |
China | 1 | <1% |
Spain | 1 | <1% |
United States | 1 | <1% |
Unknown | 317 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 81 | 25% |
Researcher | 61 | 19% |
Student > Bachelor | 37 | 11% |
Student > Master | 25 | 8% |
Student > Doctoral Student | 17 | 5% |
Other | 36 | 11% |
Unknown | 67 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 96 | 30% |
Agricultural and Biological Sciences | 72 | 22% |
Immunology and Microbiology | 41 | 13% |
Medicine and Dentistry | 22 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 7 | 2% |
Other | 23 | 7% |
Unknown | 63 | 19% |