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Activation of innate immunity by mitochondrial dsRNA in mouse cells lacking p53 protein

DM. Wiatrek, ME. Candela, J. Sedmík, J. Oppelt, LP. Keegan, MA. O'Connell,

. 2019 ; 25 (6) : 713-726. [pub] 20190320

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc19027702
E-resources Online Full text

NLK Free Medical Journals from 1995 to 6 months ago
PubMed Central from 1995 to 1 year ago
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Links

PubMed 30894411
DOI 10.1261/rna.069625.118
Knihovny.cz E-resources

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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