| First Author | Tang Q | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 9 | Pages | 1961-1975.e5 |
| PubMed ID | 34525337 | Mgi Jnum | J:323768 |
| Mgi Id | MGI:6856560 | Doi | 10.1016/j.immuni.2021.08.011 |
| Citation | Tang Q, et al. (2021) Adenosine-to-inosine editing of endogenous Z-form RNA by the deaminase ADAR1 prevents spontaneous MAVS-dependent type I interferon responses. Immunity 54(9):1961-1975.e5 |
| abstractText | Nucleic acids are powerful triggers of innate immunity and can adopt the Z-conformation, an unusual left-handed double helix. Here, we studied the biological function(s) of Z-RNA recognition by the adenosine deaminase ADAR1, mutations in which cause Aicardi-Goutieres syndrome. Adar1(mZalpha/mZalpha) mice, bearing two point mutations in the Z-nucleic acid binding (Zalpha) domain that abolish Z-RNA binding, displayed spontaneous induction of type I interferons (IFNs) in multiple organs, including in the lung, where both stromal and hematopoietic cells showed IFN-stimulated gene (ISG) induction. Lung neutrophils expressed ISGs induced by the transcription factor IRF3, indicating an initiating role for neutrophils in this IFN response. The IFN response in Adar1(mZalpha/mZalpha) mice required the adaptor MAVS, implicating cytosolic RNA sensing. Adenosine-to-inosine changes were enriched in transposable elements and revealed a specific requirement of ADAR1's Zalpha domain in editing of a subset of RNAs. Thus, endogenous RNAs in Z-conformation have immunostimulatory potential curtailed by ADAR1, with relevance to autoinflammatory disease in humans. |
