Mitochondrial double-stranded RNA triggers antiviral signalling in humans.
Mitochondrial double-stranded RNA triggers antiviral signalling in humans.
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线粒体双链RNA在人类体内触发抗病毒信号。
DOI：
10.1038/s41586-018-0363-0
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发表时间：
2018-08
期刊：
影响因子：
64.8
通讯作者：
Proudfoot NJ
中科院分区：
文献类型：
--
作者：
Dhir A;Dhir S;Borowski LS;Jimenez L;Teitell M;Rötig A;Crow YJ;Rice GI;Duffy D;Tamby C;Nojima T;Munnich A;Schiff M;de Almeida CR;Rehwinkel J;Dziembowski A;Szczesny RJ;Proudfoot NJ
Mitochondria are descendants of endosymbiotic bacteria and retain essential prokaryotic features such as a compact circular genome. Consequently, in mammals, mitochondrial DNA is subjected to bidirectional transcription that generates overlapping transcripts, which are capable of forming long double-stranded RNA structures. However, to our knowledge, mitochondrial double-stranded RNA has not been previously characterized in vivo. Here we describe the presence of a highly unstable native mitochondrial double-stranded RNA species at single-cell level and identify key roles for the degradosome components mitochondrial RNA helicase SUV3 and polynucleotide phosphorylase PNPase in restricting the levels of mitochondrial double-stranded RNA. Loss of either enzyme results in massive accumulation of mitochondrial double-stranded RNA that escapes into the cytoplasm in a PNPase-dependent manner. This process engages an MDA5-driven antiviral signalling pathway that triggers a type I interferon response. Consistent with these data, patients carrying hypomorphic mutations in the gene PNPT1, which encodes PNPase, display mitochondrial double-stranded RNA accumulation coupled with upregulation of interferon-stimulated genes and other markers of immune activation. The localization of PNPase to the mitochondrial inter-membrane space and matrix suggests that it has a dual role in preventing the formation and release of mitochondrial double-stranded RNA into the cytoplasm. This in turn prevents the activation of potent innate immune defence mechanisms that have evolved to protect vertebrates against microbial and viral attack.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1084/jem.20161451
发表时间：
2017-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Rodero MP;Decalf J;Bondet V;Hunt D;Rice GI;Werneke S;McGlasson SL;Alyanakian MA;Bader-Meunier B;Barnerias C;Bellon N;Belot A;Bodemer C;Briggs TA;Desguerre I;Frémond ML;Hully M;van den Maagdenberg AMJM;Melki I;Meyts I;Musset L;Pelzer N;Quartier P;Terwindt GM;Wardlaw J;Wiseman S;Rieux-Laucat F;Rose Y;Neven B;Hertel C;Hayday A;Albert ML;Rozenberg F;Crow YJ;Duffy D
通讯作者：
Duffy D
影响因子：
4.6
作者：
Johnson E;Seiradake E;Jones EY;Davis I;Grünewald K;Kaufmann R
通讯作者：
Kaufmann R
影响因子：
5.8
作者：
Picardi, Ernesto;Pesole, Graziano
通讯作者：
Pesole, Graziano