Journal
TRENDS IN BIOCHEMICAL SCIENCES
Volume 46, Issue 9, Pages 758-771Publisher
CELL PRESS
DOI: 10.1016/j.tibs.2021.02.002
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Funding
- EU Horizon 2020 MSCA [867470, GAR 2011101S, GAR 21-27329X]
- MEYS Inter-excellence Programme [LTC18052, GAR 19-16963S]
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Modified bases on cellular RNAs act as markers to distinguish endogenous RNA from foreign RNA, reducing innate immune responses. ADARs and other modified bases play important roles in innate immunity and cancer.
Modified bases act as marks on cellular RNAs so that they can be distinguished from foreign RNAs, reducing innate immune responses to endogenous RNA. In humans, mutations giving reduced levels of one base modification, adenosine-to-inosine deamination, cause a viral infection mimic syndrome, a congenital encephalitis with aberrant interferon induction. These Aicardi-Goutieres syndrome 6 mutations affect adenosine deaminase acting on RNA 1 (ADAR1), which generates inosines in endogenous double-stranded (ds)RNA. The inosine base alters dsRNA structure to prevent aberrant activation of antiviral cytosolic helicase RIG-I-like receptors. We review how effects of inosines, ADARs, and other modi-fied bases have been shown to be important in innate immunity and cancer.
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