Decreased A-to-I RNA editing as a source of keratinocytes’ dsRNA in psoriasis

Recognition of dsRNA molecules activates the MDA5–MAVS pathway and plays a critical role in stimulating type-I interferon
responses in psoriasis. However, the source of the dsRNA accumulation in psoriatic keratinocytes remains largely unknown. Ato-
I RNA editing is a common co- or post-transcriptional modification that diversifies adenosine in dsRNA, and leads to
unwinding of dsRNA structures. Thus, impaired RNA editing activity can result in an increased load of endogenous dsRNAs.
Here we provide a transcriptome-wide analysis of RNA editing across dozens of psoriasis patients, and we demonstrate a
global editing reduction in psoriatic lesions. In addition to the global alteration, we also detect editing changes in functional
recoding sites located in the IGFBP7, COPA, and FLNA genes. Accretion of dsRNA activates autoimmune responses, and
therefore the results presented here, linking for the first time an autoimmune disease to reduction in global editing level, are
relevant to a wide range of autoimmune diseases.