Abstract

Molecular Biology Circular RNAs (circRNAs) are expressed at low levels in tissue-specific ways in eukaryote cells. It is challenging to determine what they do because sequences of circRNAs often completely overlap with cognate linear RNAs. Liu et al. found that many circRNAs contain short double-stranded RNA (dsRNA) duplexes that repress the activation of the innate immune sensor of dsRNA—protein kinase R (PKR). On viral infection, the endonuclease RNase L globally degrades circRNAs, which releases the inhibition on PKR and triggers immune responses. Interestingly, spontaneous activation of RNase L, together with depleted circRNAs, and enhanced PKR activity are seen in immune cells isolated from patients with systemic lupus erythematosus (SLE), a common autoimmune disorder. This indicates a possibility for therapeutically relieving SLE by modulating circRNA levels. Cell 177 , 865 (2019).

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