Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response
Tatsuya Kozaki,Jun Komano,Daiki Kanbayashi,Michihiro Takahama,Michihiro Takahama,Takuma Misawa,Takashi Satoh,Osamu Takeuchi,Taro Kawai,Shigeomi Shimizu,Yoshiharu Matsuura,Shizuo Akira,Tatsuya Saitoh +12 more
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TLDR
TIPARP is a viral RNA-sensing PRR that mediates antiviral responses triggered by BAX- and BAK1-dependent mitochondrial damage and typically localizes in the nucleus, but it accumulates in the cytoplasm after SINV infection, allowing targeting of cy toplasmic SinV RNA.Abstract:
The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation. TIPARP typically localizes in the nucleus, but it accumulates in the cytoplasm after SINV infection, allowing targeting of cytoplasmic SINV RNA. Redistribution of TIPARP is induced by reactive oxygen species (ROS)-dependent oxidization of the nuclear pore that affects cytoplasmic-nuclear transport. BCL2-associated X protein (BAX) and BCL2 antagonist/killer 1 (BAK1), B-cell leukemia/lymphoma 2 (BCL2) family members, mediate mitochondrial damage to generate ROS after SINV infection. Thus, TIPARP is a viral RNA-sensing PRR that mediates antiviral responses triggered by BAX- and BAK1-dependent mitochondrial damage.read more
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Insights into the biogenesis, function, and regulation of ADP-ribosylation.
Michael S. Cohen,Paul Chang +1 more
TL;DR: The functions of amino acid ADPr modifications and the ART proteins that make them, the nature of the chemical linkage between ADPr and its targets and how this impacts function and stability, and the way that ARTs select specific amino acids in targets to modify are discussed.
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The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression.
Matthew E. Grunewald,Yating Chen,Chad V. Kuny,Takashi Maejima,Robert Lease,Dana Ferraris,Masanori Aikawa,Christopher S. Sullivan,Stanley Perlman,Anthony R. Fehr,Anthony R. Fehr +10 more
TL;DR: It is demonstrated that the macrodomain is required to prevent PARP-mediated inhibition of coronavirus replication and enhancement of interferon production, suggesting that macrodomains counter cellular ADP-ribosylation.
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The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions
Anthony R. Fehr,Sasha A Singh,Catherine M Kerr,Shin Mukai,Hideyuki Higashi,Masanori Aikawa,Masanori Aikawa +6 more
TL;DR: The current understanding of the mechanisms by which PARPs promote or suppress proinflammatory activation of macrophages, and various roles PARPs play in virus infections are given.
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Glucocorticoids, genes and brain function
TL;DR: A review of microarray reports revealed 88 genes whose transcription is consistently regulated by glucocorticoids (GCs), such as cortisol, corticosterone and dexamethasone, in the brain this article.
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PARPs and ADP-ribosylation in RNA biology: from RNA expression and processing to protein translation and proteostasis.
TL;DR: The role of PARP proteins and ADPRylation in all facets of this pathway, including gene regulation, mRNA processing, and protein abundance, is described.
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