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

J 2019

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

WIATREK-MOUMOULIDIS, Dagmara Marta, Maria Elena CANDELA, Jiří SEDMÍK, Jan OPPELT, Liam KEEGAN et. al.

Basic information

Original name

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

Authors

WIATREK-MOUMOULIDIS, Dagmara Marta (616 Poland, belonging to the institution), Maria Elena CANDELA (380 Italy, belonging to the institution), Jiří SEDMÍK (203 Czech Republic, belonging to the institution), Jan OPPELT (203 Czech Republic, belonging to the institution), Liam KEEGAN (372 Ireland, belonging to the institution) and Mary Anne O'CONNELL (372 Ireland, guarantor, belonging to the institution)

Edition

RNA, Cold Spring Harbor, Cold Spring Harbor Laboratory Press, 2019, 1355-8382

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.320

RIV identification code

RIV/00216224:14740/19:00109412

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1261/rna.069625.118

UT WoS

000468092200005

Keywords in English

mitochondrial dsRNA; p53; innate immunity; RNase L

Abstract

V originále

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.

Links

621368, interní kód MU

Name: The ERA Chair Culture as a Catalyst to Maximize the Potential of CEITEC (Acronym: CEITEC_ERA)

Investor: European Union, The ERA Chair Culture as a Catalyst to Maximize the Potential of CEITEC, Capacities

90091, large research infrastructures

Name: NCMG

Citovat

WIATREK-MOUMOULIDIS, Dagmara Marta, Maria Elena CANDELA, Jiří SEDMÍK, Jan OPPELT, Liam KEEGAN and Mary Anne O'CONNELL. Activation of innate immunity by mitochondrial dsRNA in mouse cells lacking p53 protein. RNA. Cold Spring Harbor: Cold Spring Harbor Laboratory Press, 2019, vol. 25, No 6, p. 713-726. ISSN 1355-8382. Available from: https://dx.doi.org/10.1261/rna.069625.118.

@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 and 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, 2019, vol.~25, No~6, p.~713-726. ISSN~1355-8382. Available from: https://dx.doi.org/10.1261/rna.069625.118.

Detailed Information on Publication Record