PKR-dependent cytosolic cGAS foci are necessary for intracellular DNA sensing.
Journal
Science signaling
ISSN: 1937-9145
Titre abrégé: Sci Signal
Pays: United States
ID NLM: 101465400
Informations de publication
Date de publication:
26 11 2019
26 11 2019
Historique:
entrez:
28
11
2019
pubmed:
28
11
2019
medline:
22
8
2020
Statut:
epublish
Résumé
Cyclic GMP-AMP synthase (cGAS) is a major sensor of cytosolic DNA from invading pathogens and damaged cellular organelles. Activation of cGAS promotes liquid-like phase separation and formation of membraneless cytoplasmic structures. Here, we found that cGAS bound G3BP1, a double-stranded nucleic acid helicase involved in the formation of stress granules. Loss of G3BP1 blocked subcellular cGAS condensation and suppressed the interferon response to intracellular DNA and DNA virus particles in cells. Furthermore, an RNA-dependent association with PKR promoted G3BP1 foci formation and cGAS-dependent interferon responses. Together, these results indicate that PKR promotes the formation of G3BP1-dependent, membraneless cytoplasmic structures necessary for the DNA-sensing function of cGAS in human cells. These data suggest that there is a previously unappreciated link between nucleic acid sensing pathways, which requires the formation of specialized subcellular structures.
Identifiants
pubmed: 31772125
pii: 12/609/eaav7934
doi: 10.1126/scisignal.aav7934
pii:
doi:
Substances chimiques
Poly-ADP-Ribose Binding Proteins
0
RNA Recognition Motif Proteins
0
DNA
9007-49-2
EIF2AK2 protein, human
EC 2.7.11.1
eIF-2 Kinase
EC 2.7.11.1
Nucleotidyltransferases
EC 2.7.7.-
cGAS protein, human
EC 2.7.7.-
DNA Helicases
EC 3.6.4.-
G3BP1 protein, human
EC 3.6.4.12
RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.