The Human 2′,5′-Oligoadenylate Synthetase Locus Is Composed of Three Distinct Genes Clustered on Chromosome 12q24.2 Encoding the 100-, 69-, and 40-kDa Forms

Hovnanian, Alain; Rebouillat, Dominique; Marié, Isabelle; Levy, Elaine R.; Monaco, Anthony P.; Hovanessian, Ara G.

doi:10.1006/geno.1998.5443

Cited by 79 publications

(58 citation statements)

References 61 publications

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“…A known function of 2Ј-5Ј-oligoadenylate is to bind and activate a latent endoribonuclease, RNase L, responsible for the degradation of viral and cellular single-stranded RNAs (40). 2Ј-5Ј-oligoadenylate synthetases also are involved in other cellular processes such as apoptosis, cell growth and differentiation, regulation of gene expression, DNA replication, and RNA splicing (19).…”

Section: Discussionmentioning

confidence: 99%

“…Protein sequences of mouse and human 2Ј-5Ј-oligoadenylate synthetases 2 and 3 were divided into fragments corresponding to a single functional unit (19). Multiple sequence alignments were constructed by using CLUSTAL X (20).…”

Section: Phylogenetic and Domain Architecture Analysis Of Oas Proteinsmentioning

confidence: 99%

“…The N-terminal 346 amino acids of the OAS1 protein represent one functional unit, whereas OAS2 and OAS3 contain two and three functional units, respectively (19,(34)(35)(36). The murine Oas gene sequences obtained previously by different laboratories were named without knowledge of the entire gene family and designated by different symbols.…”

Section: Phylogenetic Analysis Of the 2 -5 -Oligoadenylate Synthetasementioning

confidence: 99%

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Positional cloning of the murine flavivirus resistance gene

Perelygin

Scherbik

Zhulin

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

245

198

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Inbred mouse strains exhibit significant differences in their susceptibility to viruses in the genus Flavivirus, which includes human pathogens such as yellow fever, Dengue, and West Nile virus. A single gene, designated Flv, confers this differential susceptibility and was mapped previously to a region of mouse chromosome 5. A positional cloning strategy was used to identify 22 genes from the Flv gene interval including 10 members of the 2 -5 -oligoadenylate synthetase gene family. One 2 -5 -oligoadenylate synthetase gene, Oas1b, was identified as Flv by correlation between genotype and phenotype in nine mouse strains. Susceptible mouse strains produce a protein lacking 30% of the C-terminal sequence as compared with the resistant counterpart because of the presence of a premature stop codon. The Oas1b gene differs from all the other murine Oas genes by a unique four-amino acid deletion in the P-loop located within the conserved RNA binding domain. Expression of the resistant allele of Oas1b in susceptible embryo fibroblasts resulted in partial inhibition of the replication of a flavivirus but not of an alpha togavirus.I nnate resistance to flavivirus-induced morbidity and mortality was demonstrated in mice in the 1920s (1) and showed monogenic autosomal dominant inheritance (2). The alleles that determined resistance and susceptibility were designated Flv r and Flv s , respectively (3). Resistant mice are susceptible to infections with other types of viruses but are resistant to all flaviviruses (4). Resistant mice can be infected by flaviviruses, but the virus titers in their tissues are lower by 1,000-10,000 times than those in the tissues of susceptible animals, and the spread of the infection in resistant mice is slower (5, 6). Cell cultures derived from many different tissues of resistant mice also produce lower yields of virus; peak titers from resistant cultures are 100-1,000 times lower than those from susceptible cultures (7-9). Previous studies indicate that the Flv gene product acts intracellularly on flavivirus replication.The flavivirus-resistant allele was demonstrated in wild Mus musculus domesticus populations in both the U.S. and Australia, and flavivirus genetic resistance was reported in other Mus species (10-12). Most commonly used inbred laboratory mouse strains were derived from a small number of progenitors, and the majority of them have a homozygous flavivirus-susceptible genotype. Only the Det, BSVR, BRVR, CASA͞Rk, CAST͞Ei, MOLD͞Rk, and PRI inbred strains have the resistant allele (13). The characteristics of a resistant-like allele (designated Flv r -like) in CASA͞Rk and CAST͞Ei strains were similar to those of the PRI Flv r allele. The MOLD͞Rk animals carry an allele designated minor resistance, Flv mr , that can protect carriers from disease after infection with the attenuated 17D strain of yellow fever virus but not from the virulent Murray Valley encephalitis virus (10).The resistant allele from donor PRI mice was introduced onto the susceptible C3H͞He background to produce the co...

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Section: Discussionmentioning

confidence: 99%

Section: Phylogenetic and Domain Architecture Analysis Of Oas Proteinsmentioning

confidence: 99%

Section: Phylogenetic Analysis Of the 2 -5 -Oligoadenylate Synthetasementioning

confidence: 99%

See 1 more Smart Citation

Positional cloning of the murine flavivirus resistance gene

Perelygin

Scherbik

Zhulin

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

245

198

View full text Add to dashboard Cite

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“…IFNs are members of an important family of functionally related cytokines that participate in homeostasis, host defense, and innate immunity (4). They mediate antiviral, antiproliferative (5), antitumor (6), and immunomodulatory responses (7). A number of studies suggest that, in addition to TLR-mediated effects, other mechanisms activate the IFN response during viral infections (8).…”

Section: Iral Infection Leads To the Initiation Of Complex Innatementioning

confidence: 99%

IFN-ε Mediates TNF-α-Induced STAT1 Phosphorylation and Induction of Retinoic Acid-Inducible Gene-I in Human Cervical Cancer Cells

Matsumiya

Prescott

Stafforini

2007

The Journal of Immunology

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Retinoic acid inducible gene-I (RIG-I) plays important roles during innate immune responses to viral infections and as a transducer of cytokine signaling. The mechanisms of RIG-I up-regulation after cytokine stimulation are incompletely characterized. It was previously reported that IFN–γ induces the expression of RIG-I in endothelial cells. In this study, we characterized the mechanism of type I IFN-mediated up-regulation of RIG-I in HeLa cells and found that, in addition to type I IFN, TNF-α, a cytokine that regulates innate immune responses, induced expression of RIG-I. To investigate whether TNF-α- and type I IFN-mediated up-regulations of RIG-I were causally related, we studied the kinetics of these responses. Our results were consistent with a model in which TNF-α functioned upstream of type I IFNs. The ability of TNF-α to up-regulate RIG-I required protein synthesis, expression of functional type I IFNRs, and STAT1 signaling. We also found that IFN-ε was the only IFN isoform expressed constitutively in HeLa cells and that its expression was up-regulated in response to stimulation with TNF-α. The mechanism of up-regulation involved stabilization of IFN-ε mRNA in the absence of transcriptional activation. Silencing the expression of IFN-ε attenuated STAT1 expression and phosphorylation and inhibited RIG-I expression, providing additional support for the participation of IFN-ε upstream of STAT1. Our findings support a sequential mechanism whereby TNF-α leads to stabilization of IFN-ε mRNA, increased IFN-ε synthesis, engagement of type I IFNRs, increased STAT1 expression and phosphorylation, and up-regulation of RIG-I expression. These findings have implications for our understanding of the immune responses that follow cytokine stimulation.

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“…OAS1 contains one single domain, whereas OAS2 and OAS3 contain two and three adjacent domains, respectively. In humans, it has been shown that the three OAS genes are clustered, which might reflect their evolutionary relationship, possibly through the duplication of the conserved functional domain (Hovnanian et al, 1998). Oligoadenylate synthetases catalyze the synthesis of 2´-5´-linked oligoadenylates from ATP , which in turn can bind to the latent RNase L, which, in the presence of double stranded RNA, subsequently dimerizes into the active form.…”

Section: Fig 24: Overview Of Genes Known To Be Stimulated By Type I mentioning

confidence: 99%

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

Klein¹,

Bauersachs²,

Ulbrich³

et al. 2006

Reprod. Fertil. Dev.

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Early embryonic development, implantation, and maintenance of a pregnancy are critically dependent on an intact embryo-maternal communication. So far, only few signals involved in this dialogue have been identified. In ruminants, interferon tau (IFN�) plays a key role in the process of maternal recognition of pregnancy by exhibiting antiluteolytic activity. Even though many experimental findings indicate a pivotal role of IFN� in the context of embryo-maternal communication in ruminants, a number of other systems may be involved. To identify genes induced in the bovine endometrium by the signaling of the embryo, a combination of subtracted cDNA libraries and cDNA array hybridization was applied. Monozygotic twin pairs (n = 5) were used as the biological model. Pregnancy was created in one twin by transferring two in vitro-produced embryos on Day 7 of the estrous cycle; the other twin received a sham embryo transfer. Pregnant and nonpregnant twins were slaughtered at Day 18; endometrial tissue samples were recovered and processed for transcriptome analysis as described (Bauersachs et al. 2005 J. Mol. Endocrinol. 34, 889-908). Screening of 4608 clones of two subtracted libraries revealed 90 different up-regulated genes and mRNAs, of which almost 50% are known to be stimulated by type I interferons. Among these interferon-stimulated genes, the ISG15 system is assumed to be of particular interest, and several components were studied in more detail using in situ hybridization. The pattern of mRNA expression suggests that modification of endometrial proteins through ISG15ylation plays a fundamental role during the pre-implantation period. A classification of the identified genes based on Gene Ontologies revealed the prevalence of genes involved in regulation of gene expression, cell communication, cell growth, cell differentiation, cell proliferation, and cell adhesion, and also the prevalence of genes with immune-related functions. These results underline the intense response of the endometrium to the presence of a conceptus, culminating in the preparation of the maternal environment for embryonic implantation. Further, for eleven selected genes the expression in the endometrium was quantified by the use of real-time RT-PCR. Overall, the results of quantitative RT-PCR and array hybridization correlated very well. To our knowledge this study provides the first holistic gene expression analysis of the bovine endometrium during the pre-implantation period. The results underline the importance of IFN� as an embryo-derived pregnancy recognition signal and depict the molecular mechanisms at the mRNA level underlying the intense embryo-maternal dialog taking place at Day 18 of gestation.

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The Human 2′,5′-Oligoadenylate Synthetase Locus Is Composed of Three Distinct Genes Clustered on Chromosome 12q24.2 Encoding the 100-, 69-, and 40-kDa Forms

Cited by 79 publications

References 61 publications

Positional cloning of the murine flavivirus resistance gene

Positional cloning of the murine flavivirus resistance gene

IFN-ε Mediates TNF-α-Induced STAT1 Phosphorylation and Induction of Retinoic Acid-Inducible Gene-I in Human Cervical Cancer Cells

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

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