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

Lea Shallev, Eli Kopel, Ariel Feiglin, Gil S. Leichner, Dror Avni, Yechezkel Sidi, Eli Eisenberg, Aviv Barzilai, Erez Y. Levanon, Shoshana Greenberger

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish
Pages (from-to)828-840
Number of pages13
Issue number6
StatePublished - Jun 2018

Bibliographical note

Funding 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.).

Publisher Copyright:
© 2018 Shallev et al.


  • A-to-I
  • Interferon
  • Psoriasis
  • RNA editing


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