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@article{1517696,
author = {WiatrekandMoumoulidis, Dagmara Marta and Candela, Maria Elena and Sedmík, Jiří and Oppelt, Jan and Keegan, Liam and O'Connell, Mary Anne},
article_location = {Cold Spring Harbor},
article_number = {6},
doi = {http://dx.doi.org/10.1261/rna.069625.118},
keywords = {mitochondrial dsRNA; p53; innate immunity; RNase L},
language = {eng},
issn = {1355-8382},
journal = {RNA},
title = {Activation of innate immunity by mitochondrial dsRNA in mouse cells lacking p53 protein},
url = {http://dx.doi.org/10.1261/rna.069625.118},
volume = {25},
year = {2019}
}
TY - JOUR
ID - 1517696
AU - Wiatrek-Moumoulidis, Dagmara Marta - Candela, Maria Elena - Sedmík, Jiří - Oppelt, Jan - Keegan, Liam - O'Connell, Mary Anne
PY - 2019
TI - Activation of innate immunity by mitochondrial dsRNA in mouse cells lacking p53 protein
JF - RNA
VL - 25
IS - 6
SP - 713-726
EP - 713-726
PB - Cold Spring Harbor Laboratory Press
SN - 13558382
KW - mitochondrial dsRNA
KW - p53
KW - innate immunity
KW - RNase L
UR - http://dx.doi.org/10.1261/rna.069625.118
L2 - http://dx.doi.org/10.1261/rna.069625.118
N2 - 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.
ER -
WIATREK-MOUMOULIDIS, Dagmara Marta, Maria Elena CANDELA, Jiří SEDMÍK, Jan OPPELT, Liam KEEGAN a Mary Anne O'CONNELL. Activation of innate immunity by mitochondrial dsRNA in mouse cells lacking p53 protein. \textit{RNA}. Cold Spring Harbor: Cold Spring Harbor Laboratory Press, roč.~25, č.~6, s.~713-726. ISSN~1355-8382. doi:10.1261/rna.069625.118. 2019.
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