Multiple cytosolic DNA sensors bind plasmid DNA after transfection.
Animals
Cell Line
Cytosol
/ metabolism
DEAD-box RNA Helicases
/ genetics
DNA
/ genetics
DNA-Binding Proteins
/ genetics
Gene Expression Regulation
/ genetics
Humans
Interferon Type I
/ genetics
Mice
Nuclear Proteins
/ genetics
Phosphoproteins
/ genetics
Plasmids
/ genetics
RNA, Messenger
/ genetics
RNA-Binding Proteins
/ genetics
Signal Transduction
/ genetics
Transfection
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
04 11 2019
04 11 2019
Historique:
accepted:
22
08
2019
received:
11
07
2019
pubmed:
10
9
2019
medline:
18
12
2019
entrez:
10
9
2019
Statut:
ppublish
Résumé
Mammalian cells express a variety of nucleic acid sensors as one of the first lines of defense against infection. Despite extensive progress in the study of sensor signaling pathways during the last decade, the detailed mechanisms remain unclear. In our previous studies, we reported increased type I interferon expression and the upregulation of several proposed cytosolic DNA sensors after transfection of several tumor cell types with plasmid DNA (pDNA). In the present study, we sought to reveal the early events in the cytosolic sensing of this nucleic acid in a myoblast cell line. We demonstrated that DNA-dependent activator of interferon regulatory factors/Z-DNA binding protein 1 (DAI/ZBP1) bound plasmid DNA in the cytosol within 15 minutes of transfection and at consistent levels for 4 h. Interferon activated gene 204 protein (p204) and DEAH box helicase 9 (DHX9) also bound pDNA, peaking 15 and 30 min respectively. Plasmid DNA was not detectably bound by DEAD box helicase 60 (DDX60) protein, despite a similar level of mRNA upregulation to DAI/ZBP1, or by cyclic GMP-AMP synthase (cGAS), despite its presence in the cell cytosol. Taken together, these results indicate several DNA sensors may participate and cooperate in the complex process of cytosolic DNA sensing.
Identifiants
pubmed: 31495892
pii: 5565289
doi: 10.1093/nar/gkz768
pmc: PMC6821305
doi:
Substances chimiques
DNA-Binding Proteins
0
Dhx9 protein, mouse
0
Ifi16 protein, mouse
0
Interferon Type I
0
Nuclear Proteins
0
Phosphoproteins
0
RNA, Messenger
0
RNA-Binding Proteins
0
Zbp1 protein, mouse
0
DNA
9007-49-2
DDX60 protein, mouse
EC 3.6.1.-
DEAD-box RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
10235-10246Subventions
Organisme : NCI NIH HHS
ID : R01 CA196796
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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