OAS1 and OAS3 negatively regulate the expression of chemokines and interferon-responsive genes in human macrophages.
- OAS1 and OAS3 negatively regulate the expression of chemokines and interferon-responsive genes in human macrophages.
- 이욱빈; 최원영; 이동현; 심혜란; 하정실; 김영준
- Issue Date
- BMB REPORTS
- VOL 52, NO 2-138
- Upon viral infection, the 2’, 5’-oligoadenylate synthetase
(OAS)-ribonuclease L (RNaseL) system works to cleave viral
RNA, thereby blocking viral replication. However, it is unclear
whether OAS proteins have a role in regulating gene expression.
Here, we show that OAS1 and OAS3 act as negative
regulators of the expression of chemokines and interferonresponsive
genes in human macrophages. Clustered regularly
interspaced short palindromic repeats (CRISPR)-CRISPR-associated
protein-9 nuclease (Cas9) technology was used to engineer
human myeloid cell lines in which the OAS1 or OAS3 gene
was deleted. Neither OAS1 nor OAS3 was exclusively
responsible for the degradation of rRNA in macrophages
stimulated with poly(I:C), a synthetic surrogate for viral
double-stranded (ds)RNA. An mRNA sequencing analysis
revealed that genes related to type I interferon signaling and
chemokine activity were increased in OAS1− /− and OAS3− macrophages treated with intracellular poly(I:C). Indeed,
retinoic-acid-inducible gene (RIG)-I- and interferon-induced
helicase C domain-containing protein (IFIH1 or MDA5)-mediated
induction of chemokines and interferon-stimulated genes was
regulated by OAS3, but Toll-like receptor 3 (TLR3)- and
TLR4-mediated induction of those genes was modulated by
OAS1 in macrophages. However, stimulation of these cells
with type I interferons had no effect on OAS1- or OAS3-
mediated chemokine secretion. These data suggest that OAS1
and OAS3 negatively regulate the expression of chemokines
and interferon-responsive genes in human macrophages.
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