Activation of innate immunity by mitochondrial dsRNA in mouse cells lacking p53 protein
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F19%3A00109412" target="_blank" >RIV/00216224:14740/19:00109412 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1261/rna.069625.118" target="_blank" >http://dx.doi.org/10.1261/rna.069625.118</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1261/rna.069625.118" target="_blank" >10.1261/rna.069625.118</a>
Alternative languages
Result language
angličtina
Original language name
Activation of innate immunity by mitochondrial dsRNA in mouse cells lacking p53 protein
Original language 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LM2015091" target="_blank" >LM2015091: National Center for Medical Genomic</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
RNA
ISSN
1355-8382
e-ISSN
1469-9001
Volume of the periodical
25
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
713-726
UT code for WoS article
000468092200005
EID of the result in the Scopus database
2-s2.0-85066118492