ADAR1 editing in cellular transcripts sets an immune-activation threshold for dsRNA.

(A) Quantification of ADAR1-edited transcripts (order as in S1 Table) in HeLa, p150KO, and ADAR1KO cells. Four conditions were analyzed for each cell type: UI, infected with MeV-vac2(GFP), infected with MeV-CKO(GFP) (both at MOI = 3 for 24 h), or treated with IFN A/D (1,000 U/ml for 24 h). Heatmap shows log10 FPKM values from RNAseq analysis. (B) Normalized expression levels of ADAR1-edited transcripts relative to GAPDH levels. Median levels for the four conditions described in (A) are shown. Error bars indicate 95% confidence interval. (C) Proportion of ADAR1-edited (red) and nonedited (gray) in HeLa, p150KO, and ADAR1KO cells. (D) Coverage plots and location of ADAR1 editing relative to annotated transcript 3′ end (blue dashed line). Editing occurs between red triangles. Black dot indicates CDS stop codon. (E) Comparison of ADAR1-edited transcripts identified by us (green, cyan, yellow, white), Chung and colleagues [34] (blue, cyan, magenta, white), and Ahmad and colleagues [42] (red, magenta, yellow, white). Each transcript is represented by a single tile. The total numbers in each group (unique, shared by two or three independent studies) are indicated in the legend to the lower right. ADAR1, adenosine deaminase acting on RNA 1; ADAR1KO, fully ADAR1-deficient; CDS, coding sequence; dsRNA, double-stranded RNA; FPKM, fragments per kilobase of transcript per million mapped reads; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; IFN A/D, recombinant type-I interferon-alpha; MOI, multiplicity of infection; NT, nucleotide; p150KO, selectively ADAR1p150-deficient; RNAseq, RNA sequencing; UI, uninfected.