Structure of two forms of the interferon-induced (2′-5′) oligo A synthetase of human cells based on cDNAs and gene sequences.

Abstract

The (2′‐5′) oligo A synthetase E, one of the translational inhibitory enzymes whose synthesis is strongly induced by all interferons (IFNs), is shown to be encoded in human cells by a 13.5‐kb gene. By a cell‐specific differential splicing, between the seventh and an additional eighth exon of this gene, two active E mRNAs of 1.6 and 1.8 kb are produced, along with several longer transcripts. cDNA clones for the two mRNAs were obtained and their sequences indicate that the human (2′‐5′) oligo A synthetase gene codes for two forms of the enzyme of mol. wt. 41 000 and 46 000, which differ only by their C‐terminal ends. The product of the 1.6‐kb RNA (E16) has a very hydrophobic C terminus, which is replaced by a longer acidic C‐terminal sequence in the 1.8‐kb RNA product (E18). The transcriptional start site of the gene was identified and 200 bp of the 5′ flanking region were sequenced. A strong homology was found between this region of the IFN‐activated (2′‐5′) oligo A synthetase gene and the corresponding region of the human fibroblast IFN‐beta 1 gene, whose transcription is also stimulated by IFN priming. The gene has two polyadenylation sites which share a common undecanucleotide, but are used in a cell‐specific manner to give rise to the 1.6‐ and 1.8‐kb mRNAs.

Synergism of type I and type II Interferons in stimulating the activity of the same DNA enhancer

“…The two types of IFNs differ, however, notably in their structure, their cell surface receptors, and their biological activities [2,3]. It is therefore logical that the characteristics of induction of the cloned 2-SA synthetase mRNAs [4] by the two IFNs are not similar [5,6]. The mRNAs are induced much less by IFNy than by type I IFNs [5,6].…”

Effect of Interferon on the Accumulation of RNA Transcripts of Genes Coding for Cellular and Viral Proteins

“…The activated nuclease hydrolyses mRNA and therefore protein synthesis is inhibited in interferon-treated cells (Kerr & Brown, 1978;Slattery et al, 1979). Oligo-2',5'-adenylate synthetase (2-5AS) has been fully characterized and its gene has been cloned (Benech et al, 1985;Merlin et al, 1983). It is therefore now possible to use a plasmid with sequences from the 2-5AS gene to study directly the levels of its expression in control, virus-infected or interferon-treated cells.…”

New inducers revealed by the promoter sequence analysis of two interferon-activated human genes

“…In that way interferons, as other cytokines, act as pleiotropic effectors, since they modify not only the biochemistry of some target cells but also the physiology of the entire organism. Conversely it has been suggested that some other cytokines (tumor necrosis factors c( and p [3,41) have intrinsic antiviral activities.Numerous cDNAs corresponding to interferon-inducible genes have been cloned but the biological function of these genes has been discovered in a few cases only. Their transcriptional regulation appears to be rather complex.…”

“…Beside the establishment of an antiviral state, interaction between interferon and its receptor on the cell surface also leads to a wide range of biological effects, such as the inhibition of cell growth and modulations of the immune system (for reviews see [l, 21. In that way interferons, as other cytokines, act as pleiotropic effectors, since they modify not only the biochemistry of some target cells but also the physiology of the entire organism. Conversely it has been suggested that some other cytokines (tumor necrosis factors c( and p [3,41) have intrinsic antiviral activities.…”

“…In that way interferons, as other cytokines, act as pleiotropic effectors, since they modify not only the biochemistry of some target cells but also the physiology of the entire organism. Conversely it has been suggested that some other cytokines (tumor necrosis factors c( and p [3,41) have intrinsic antiviral activities.…”