Imperial College London
Professor Caetano Reis e Sousa

ProfessorCaetanoReis e Sousa

Faculty of Medicine, Department of Immunology and Inflammation

Visiting Professor
 
 
 
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Contact

 

c.reisesousa

 
 
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Location

 

Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Stok:2021:10.1101/2021.10.27.465188,
author = {Stok, JE and Oosenbrug, T and ter, Haar LR and Gravekamp, D and Bromley, CP and Zelenay, S and Reis, e Sousa C and van, der Veen AG},
doi = {10.1101/2021.10.27.465188},
title = {RNA sensing via LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency},
url = {http://dx.doi.org/10.1101/2021.10.27.465188},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>RNA editing by the enzyme Adenosine Deaminase Acting on RNA 1 (ADAR1) is an important mechanism by which cells avoid innate immune responses to some endogenous RNAs. In ADAR1-deficient cells, unedited self RNAs can form base-paired structures that resemble viral RNAs and inadvertently activate antiviral innate immune pathways that lead to the induction of type I interferon (IFN). Rare mutations in ADAR1 cause Aicardi-Goutières Syndrome (AGS), a severe childhood autoinflammatory syndrome that is characterized by chronic and excessive type I IFN production and developmental delay. Conversely, ADAR1 dysfunction and consequent type I IFN production helps restrict tumor growth and potentiates the activity of some chemotherapy drugs. Induction of type I IFN in ADAR1-deficient cells is thought to be due to triggering of the cytosolic RIG-I-like receptor (RLR), MDA5, by unedited self RNAs. Here, we show that another RLR, LGP2, also has an essential role. We demonstrate that ADAR1-deficient human cells fail to mount a type I IFN response in the absence of LGP2 and this involves the canonical function of LGP2 as an RNA sensor and facilitator of MDA5-dependent signaling. Further, we show that the sensitivity of tumor cells to ADAR1 loss requires the presence of LGP2. Finally, we find that type I IFN induction in tumor cells depleted of ADAR1 and treated with some chemotherapeutics is fully dependent on the expression of LGP2. These findings highlight a central role for LGP2 in self RNA sensing with important clinical implications for the treatment of AGS as well as for the potential application of ADAR1-directed anti-tumor therapy.</jats:p>
AU  - Stok,JE
AU  - Oosenbrug,T
AU  - ter,Haar LR
AU  - Gravekamp,D
AU  - Bromley,CP
AU  - Zelenay,S
AU  - Reis,e Sousa C
AU  - van,der Veen AG
DO  - 10.1101/2021.10.27.465188
PY  - 2021///
TI  - RNA sensing via LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency
UR  - http://dx.doi.org/10.1101/2021.10.27.465188
ER  -
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