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

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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.