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

RNA. 2018 Jun;24(6):828-840. doi: 10.1261/rna.064659.117. Epub 2018 Mar 28.


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.

Keywords: A-to-I; RNA editing; interferon; psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / genetics*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cells, Cultured
  • Connective Tissue Growth Factor / genetics
  • Copper-Transporting ATPases / genetics
  • Escherichia coli Proteins / genetics
  • Female
  • Filamins / genetics
  • Gene Expression Profiling
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Inosine / genetics*
  • Keratinocytes / cytology
  • Keratinocytes / immunology
  • Keratinocytes / metabolism*
  • Male
  • Middle Aged
  • Psoriasis / genetics*
  • Psoriasis / immunology
  • Psoriasis / pathology
  • RNA Editing*
  • RNA, Double-Stranded*
  • Young Adult


  • CCN2 protein, human
  • Escherichia coli Proteins
  • FLNA protein, human
  • Filamins
  • RNA, Double-Stranded
  • Connective Tissue Growth Factor
  • Inosine
  • Copper-Transporting ATPases
  • copA protein, E coli
  • Adenosine