Activation of innate immunity by mitochondrial dsRNA in mouse cells lacking p53 protein.
RNA
; 25(6): 713-726, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30894411
ABSTRACT
Viral and cellular double-stranded RNA (dsRNA) is recognized by cytosolic innate immune sensors, including RIG-I-like receptors. Some cytoplasmic dsRNA is commonly present in cells, and one source is mitochondrial dsRNA, which results from bidirectional transcription of mitochondrial DNA (mtDNA). Here we demonstrate that Trp53 mutant mouse embryonic fibroblasts contain immune-stimulating endogenous dsRNA of mitochondrial origin. We show that the immune response induced by this dsRNA is mediated via RIG-I-like receptors and leads to the expression of type I interferon and proinflammatory cytokine genes. The mitochondrial dsRNA is cleaved by RNase L, which cleaves all cellular RNA including mitochondrial mRNAs, increasing activation of RIG-I-like receptors. When mitochondrial transcription is interrupted there is a subsequent decrease in this immune-stimulatory dsRNA. Our results reveal that the role of p53 in innate immunity is even more versatile and complex than previously anticipated. Our study, therefore, sheds new light on the role of endogenous RNA in diseases featuring aberrant immune responses.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA de Cadeia Dupla
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Adenosina Desaminase
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Proteína Supressora de Tumor p53
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Proteína DEAD-box 58
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RNA Mitocondrial
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Imunidade Inata
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article