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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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
JournalRNA
Volume24
Issue number6
DOIs
StatePublished - Jun 2018

Funding

FundersFunder number
Talpiot Medical Leadership Program
Seventh Framework Programme311257
European Research Council
Japan Science and Technology Agency10765-3
Israel Science Foundation379/ 12, 1380/14
Ministry of Science and Technology, Israel

    Keywords

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

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