Publication details

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

Authors

WIATREK-MOUMOULIDIS Dagmara Marta CANDELA Maria Elena SEDMÍK Jiří OPPELT Jan KEEGAN Liam O'CONNELL Mary Anne

Year of publication 2019
Type Article in Periodical
Magazine / Source RNA
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://dx.doi.org/10.1261/rna.069625.118
Doi http://dx.doi.org/10.1261/rna.069625.118
Keywords mitochondrial dsRNA; p53; innate immunity; RNase L
Description 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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