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.
- MeSH
- adenosindeaminasa nedostatek genetika imunologie MeSH
- DEAD box protein 58 genetika imunologie MeSH
- dvouvláknová RNA genetika imunologie MeSH
- embryo savčí MeSH
- endoribonukleasy genetika imunologie MeSH
- fibroblasty cytologie imunologie MeSH
- genetická transkripce MeSH
- IFIH1 genetika imunologie MeSH
- interferonový regulační faktor 7 genetika imunologie MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- nádorový supresorový protein p53 nedostatek genetika imunologie MeSH
- přirozená imunita genetika MeSH
- proteiny genetika imunologie MeSH
- RNA mitochondriální genetika imunologie MeSH
- transfekce MeSH
- transportní proteiny genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
