1.Oligoadenylate synthase-like (OASL) proteins: dual functions and associations with diseases.
Un Yung CHOI ; Ji Seon KANG ; Yune Sahng HWANG ; Young Joon KIM
Experimental & Molecular Medicine 2015;47(3):e144-
The study of antiviral pathways to reveal methods for the effective response and clearance of virus is closely related to understanding interferon (IFN) signaling and its downstream target genes, IFN-stimulated genes. One of the key antiviral factors induced by IFNs, 2'-5' oligoadenylate synthase (OAS), is a well-known molecule that regulates the early phase of viral infection by degrading viral RNA in combination with RNase L, resulting in the inhibition of viral replication. In this review, we describe OAS family proteins from a different point of view from that of previous reviews. We discuss not only RNase L-dependent (canonical) and -independent (noncanonical) pathways but also the possibility of the OAS family members as biomarkers for various diseases and clues to non-immunological functions based on recent studies. In particular, we focus on OASL, a member of the OAS family that is relatively less well understood than the other members. We will explain its anti- and pro-viral dual roles as well as the diseases related to single-nucleotide polymorphisms in the corresponding gene.
2',5'-Oligoadenylate Synthetase/*genetics/*metabolism
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Animals
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Biomarkers
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*Disease Susceptibility
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Endoribonucleases/metabolism
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Genetic Predisposition to Disease
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Humans
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Multigene Family
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Polymorphism, Single Nucleotide
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Signal Transduction
2.Cloning, expression and functional analysis of the duck Toll-like receptor 5 (TLR5) gene.
Yuqiang CHENG ; Yingjie SUN ; Hengan WANG ; Shuduan SHI ; Yaxian YAN ; Jing LI ; Chan DING ; Jianhe SUN
Journal of Veterinary Science 2015;16(1):37-46
Toll-like receptor 5 (TLR5) is responsible for the recognition of bacterial flagellin in vertebrates. In the present study, the first TLR5 gene in duck was cloned. The open reading frame (ORF) of duck TLR5 (dTLR5) cDNA is 2580 bp and encodes a polypeptide of 859 amino acids. We also cloned partial sequences of myeloid differentiation factor 88, 2'-5'-oligoadenylate synthetase (OAS), and myxovirus resistance (Mx) genes from duck. dTLR5 mRNA was highly expressed in the bursa of Fabricius, spleen, trachea, lung, jejunum, rectum, and skin; moderately expressed in the muscular and glandular tissues, duodenum, ileum, caecum, and pancreas; and minimally expressed in the heart, liver, kidney, and muscle. DF-1 or HeLa cells transfected with DNA constructs encoding dTLR5 can activate NF-kappaB leading to the activation of interleukin-6 (IL-6) promoter. When we challenged ducks with a Herts33 Newcastle disease virus (NDV), mRNA transcription of the antiviral molecules Mx, Double stranded RNA activated protein kinase (PKR), and OAS was up-regulated in the liver, lung, and spleen 1 and 2 days post-inoculation.
2',5'-Oligoadenylate Synthetase/genetics/metabolism
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Animals
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Cell Line
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*Cloning, Molecular
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Ducks
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Gene Expression Regulation/*physiology
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Humans
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Immunity, Innate
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Myeloid Differentiation Factor 88/genetics/metabolism
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Myxovirus Resistance Proteins/genetics/metabolism
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Newcastle Disease/metabolism
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Newcastle disease virus/classification
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RNA, Messenger/genetics/metabolism
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Species Specificity
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Toll-Like Receptor 5/genetics/*metabolism
3.Study of the effect of hepatitis C virus core protein on interferon-induced antiviral genes expression and its mechanisms.
Yan-Zi CHANG ; Yan-Chang LEI ; You-Hua HAO ; Shan-Shan CHEN ; Wen WU ; Dong-Liang YANG ; Meng-Ji LU
Chinese Journal of Biotechnology 2007;23(6):1000-1004
To study the effect of HCV core protein on the interferon-induced antiviral genes expression and its mechanisms. Methods HepG2 cells were transiently transfected with HCV core protein expression plasmid and the blank plasmid respectively. RT-PCR was used to analyze the effect of HCV core protein on PKR and 2'-5'OAS expression. The effect of HCV core protein on ISRE-medicated gene expression was detected by luciferase activity assay. Western-blot assay was performed to observe the change of mRNA and protein levels of SOCS3, STAT1 and p-STAT1 following HCV core expression. In the presence of HCV core protein, the transcription of PKR and 2'-5' OAS are down-regulated. ISRE-medicated reporter gene expression and STAT1 phosphorylation were inhibited. The transcription and expression of SOCS3 were induced compared with blank plasmid-transfected group. In HepG2 cells, HCV core protein can down-regulate the expression of some interferon-induced antiviral genes, which involves the induction of SOCS3 and the inhibition of STAT1 phosphorylation.
2',5'-Oligoadenylate Synthetase
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genetics
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metabolism
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Carcinoma, Hepatocellular
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pathology
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Down-Regulation
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Hepacivirus
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genetics
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metabolism
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Humans
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Interferon-Stimulated Gene Factor 3
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genetics
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metabolism
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Interferon-alpha
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genetics
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immunology
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Liver Neoplasms
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pathology
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Protein Kinases
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genetics
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metabolism
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STAT1 Transcription Factor
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genetics
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metabolism
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STAT2 Transcription Factor
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genetics
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metabolism
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Transcription, Genetic
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Transfection
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Tumor Cells, Cultured
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Viral Core Proteins
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genetics
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metabolism
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physiology