Lee, Wook-Bin Choi, Won Young Lee, Dong-Hyun Shim, Hyeran Kim-Ha, Jeongsil Kim, Young-Joon 2024-01-19T20:33:58Z 2024-01-19T20:33:58Z 2021-09-02 2019-02-28 1976-6696 https://pubs.kist.re.kr/handle/201004/120321 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 interferon-responsive 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. English KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY RNASE-L VIRUS-INFECTION RECOGNITION ACTIVATION POLYMORPHISMS ASSOCIATION RECEPTORS MECHANISM IMMUNITY OAS1 and OAS3 negatively regulate the expression of chemokines and interferon-responsive genes in human macrophages Article 10.5483/BMBRep.2019.52.2.129 1 BMB REPORTS, v.52, no.2, pp.133 - 138 BMB REPORTS 52 2 133 138 scie scopus kci ART002440845 000459934900006 2-s2.0-85062379043 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article RNASE-L VIRUS-INFECTION RECOGNITION ACTIVATION POLYMORPHISMS ASSOCIATION RECEPTORS MECHANISM IMMUNITY Macrophage Negative regulation OAS poly(I:C) RNA degradation