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. A-to-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.
|Number of pages||13|
|State||Published - Jun 2018|
Bibliographical noteFunding Information:
We thank Hagit Porath, Lily Bazak, and Yishay Pinto for assisting with the computational analysis and Orshay Gabay for the graphical help. This work was supported by the Ministry of Science and Technology, Israel, the Japan Science and Technology Agency (JST) (10765-3 to E.Y.L), the European Research Council (311257 to E.Y.L.), the Israel Science Foundation (1380/14 to E.Y.L., 379/ 12 to E.E.), and the Talpiot Medical leadership program (to S.G.).
© 2018 Shallev et al.
- RNA editing