Decreased A-to-I RNA editing as a source of keratinocytes' dsRNA in psoriasis.
RNA
; 24(6): 828-840, 2018 06.
Article
em En
| MEDLINE
| ID: mdl-29592874
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psoríase
/
RNA de Cadeia Dupla
/
Queratinócitos
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Adenosina
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Edição de RNA
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Inosina
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
/
Aged80
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Female
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Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
RNA
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Israel