A conserved miRNA-183 cluster regulates the innate antiviral response.
J Biol Chem
; 294(51): 19785-19794, 2019 12 20.
Article
en En
| MEDLINE
| ID: mdl-31694919
ABSTRACT
Upon immune recognition of viruses, the mammalian innate immune response activates a complex signal transduction network to combat infection. This activation requires phosphorylation of key transcription factors regulating IFN production and signaling, including IFN regulatory factor 3 (IRF3) and STAT1. The mechanisms regulating these STAT1 and IRF3 phosphorylation events remain unclear. Here, using human and mouse cell lines along with gene microarrays, quantitative RT-PCR, viral infection and plaque assays, and reporter gene assays, we demonstrate that a microRNA cluster conserved among bilaterian animals, encoding miR-96, miR-182, and miR-183, regulates IFN signaling. In particular, we observed that the miR-183 cluster promotes IFN production and signaling, mediated by enhancing IRF3 and STAT1 phosphorylation. We also found that the miR-183 cluster activates the IFN pathway and inhibits vesicular stomatitis virus infection by directly targeting several negative regulators of IRF3 and STAT1 activities, including protein phosphatase 2A (PPP2CA) and tripartite motif-containing 27 (TRIM27). Overall, our work reveals an important role of the evolutionarily conserved miR-183 cluster in the regulation of mammalian innate immunity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Familia de Multigenes
/
MicroARNs
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Factor de Transcripción STAT1
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Factor 3 Regulador del Interferón
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Inmunidad Innata
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2019
Tipo del documento:
Article
País de afiliación:
Canadá