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

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

Author information

1
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
2
The Department of Dermatology, Sheba Medical Center, Tel Hashomer 52621, Israel.
3
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
4
Department of Medicine C, Sheba Medical Center, Tel Hashomer 52621, Israel.
5
Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv 69978, Israel.
6
Talpiot Medical Leadership Program, Sheba Medical Center, Tel Hashomer 52621, Israel.

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.

KEYWORDS:

A-to-I; RNA editing; interferon; psoriasis

PMID:
29592874
PMCID:
PMC5959251
[Available on 2019-06-01]
DOI:
10.1261/rna.064659.117
[Indexed for MEDLINE]

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