Showing papers on "Exon published in 1989"
TL;DR: The 70 published sequences of group II introns from fungal and plant mitochondria and plant chloroplasts are analyzed for conservation of primary sequence, secondary structure and three-dimensional base pairings.
714 citations
TL;DR: In this review, the discussion of mechanisms attempts to be exhaustive, drawing not only upon direct experimental investigations of alternatively spliced genes, but also upon relevant themes derived from the study of constitutive splicing.
Abstract: In this review, we focus upon the mechanistic, functional, and evolutionary aspects of alternative splicing. The discussion of mechanisms attempts to be exhaustive, drawing not only upon direct experimental investigations of alternatively spliced genes, but also upon relevant themes derived from the study of constitutive splicing
641 citations
TL;DR: Characterization of the growth hormone receptor gene from nine patients with Laron-type dwarfism shows that two individuals have a deletion of a large portion of the extracellular, hormone binding domain of the receptor gene.
Abstract: Laron-type dwarfism is an autosomal recessive genetic disorder that is characterized by high levels of growth hormone and low levels of insulin-like growth factor I in the circulation. Several lines of evidence suggest that this disease is caused by a defect in the growth hormone receptor. In order to analyze the receptor gene in patients with Laron-type dwarfism and with other growth disorders, we have first determined the gene structure in normal individuals. There are nine exons that encode the receptor and several additional exons in the 5' untranslated region. The coding exons span at least 87 kilobase pairs of chromosome 5. Characterization of the growth hormone receptor gene from nine patients with Laron-type dwarfism shows that two individuals have a deletion of a large portion of the extracellular, hormone binding domain of the receptor gene. Interestingly, this deletion includes nonconsecutive exons, suggesting that an unusual rearrangement may have occurred. Thus, we provide direct evidence that Laron-type dwarfism can result from a defect in the structural gene for the growth hormone receptor.
591 citations
TL;DR: The results support the conclusion that para encodes a functionally predominant class of sodium channels in Drosophila neurons and the para transcript appears to undergo alternative splicing to produce several distinct subtypes of this channel.
519 citations
Journal Article•
TL;DR: The combination of cDNA hybridizations with long-range analysis of deletion and duplication patients yields a global picture of the exon spacing within the dystrophin gene.
Abstract: We have studied 34 Becker and 160 Duchenne muscular dystrophy (DMD) patients with the dystrophin cDNA, using conventional blots and FIGE analysis. One hundred twenty-eight mutations (65%) were found, 115 deletions and 13 duplications, of which 106 deletions and 11 duplications could be precisely mapped in relation to both the mRNA and the major and minor mutation hot spots. Junction fragments, ideal markers for carrier detection, were found in 23 (17%) of the 128 cases. We identified eight new cDNA RFLPs within the DMD gene. With the use of cDNA probes we have completed the long-range map of the DMD gene, by the identification of a 680-kb SfiI fragment containing the gene's 3' end. The size of the DMD gene is now determined to be about 2.3 million basepairs. The combination of cDNA hybridizations with long-range analysis of deletion and duplication patients yields a global picture of the exon spacing within the dystrophin gene. The gene shows a large variability of intron size, ranging from only a few kilobases to 160-180 kb for the P20 intron.
505 citations
Journal Article•
TL;DR: To identify possible regulatory sites of the gene expression, the genomic DNA of human monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8), whose mRNA is induced by IL-1 or TNF was cloned and its entire nucleotide sequence was determined.
Abstract: To identify possible regulatory sites of the gene expression, we cloned the genomic DNA of human monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8), whose mRNA is induced by IL-1 or TNF and determined its entire nucleotide sequence. The results show that the MDNCF/IL-8 gene consists of 4 exons and 3 introns with a single "CAT"- and "TATA"-like structure. The 5'-flanking region of MDNCF/IL-8 gene shows no overall sequence similarity with that of other cytokine and acute phase reactant genes whose production is also affected by IL-1 and TNF. The 5' flanking region, however, contains potential binding sites for several nuclear factors including activation factor-1, activation factor-2, IFN regulatory factor-1, and hepatocyte nuclear factor-1. In addition, the glucocorticoid responsive element and heat shock element were located in the 5'-flanking region. Inasmuch as PMA induces MDNCF/IL-8 mRNA accumulation in human PBMC and a glucocorticoid inhibits the induction of MDNCF/IL-8 mRNA by LPS, the expression of this gene is probably regulated by interaction of these nuclear factors with the 5'-flanking DNA.
500 citations
TL;DR: In this paper, a human D2 dopamine receptor was sequenced from a pituitary cDNA library and sequenced with the deduced protein sequence is 96% identical with that of the cloned rat receptor with one major difference: the human receptor contains an additional 29 amino acids in its putative third cytoplasmic loop.
Abstract: A clone encoding a human D2 dopamine receptor was isolated from a pituitary cDNA library and sequenced. The deduced protein sequence is 96% identical with that of the cloned rat receptor with one major difference: the human receptor contains an additional 29 amino acids in its putative third cytoplasmic loop. Southern blotting demonstrated the presence of only one human D2 receptor gene. Two overlapping phage containing the gene were isolated and characterized. DNA sequence analysis of these clones showed that the coding sequence is interrupted by six introns and that the additional amino acids present in the human pituitary receptor are encoded by a single exon of 87 base pairs. The involvement of this sequence in alternative splicing and its biological significance are discussed.
475 citations
TL;DR: A number of repetitive sequences were identified including 14 Alu repeats and a approximately 670-base pair TCTA simple repeat in intron 40 that is polymorphic.
460 citations
TL;DR: The putative proteins encoded by CYP11B1 and B2 each contain 503 amino acids including a 24-residue signal peptide and have sequences that are 93% identical to each other and 75% identicalto the predicted sequence of bovine P-450(11) beta.
457 citations
TL;DR: A single point mutation in the steroid-binding domain of the AR gene correlated with the expression of an AR protein ineffective in stimulating male sexual development.
Abstract: Androgens act through a receptor protein (AR) to mediate sex differentiation and development of the male phenotype. We have isolated the eight exons in the amino acid coding region of the AR gene from a human X chromosome library. Nucleotide sequences of the AR gene intron/exon boundaries were determined for use in designing synthetic oligonucleotide primers to bracket coding exons for amplification by the polymerase chain reaction. Genomic DNA was amplified from 46,XY phenotypic female siblings with complete androgen insensitivity syndrome. AR binding affinity for dihydrotestosterone in the affected siblings was lower than in normal males, but the binding capacity was normal. Sequence analysis of amplified exons demonstrated within the AR steroid-binding domain (exon G) a single guanine to adenine mutation, resulting in replacement of valine with methionine at amino acid residue 866. As expected, the carrier mother had both normal and mutant AR genes. Thus, a single point mutation in the steroid-binding domain of the AR gene correlated with the expression of an AR protein ineffective in stimulating male sexual development.
456 citations
TL;DR: The whole length of the human preproendothelin-1 gene and the corresponding cDNA and the complete nucleotide sequences are cloned and suggest that the regulation of expression of PPET-1 mRNA may be mediated in part by these sequence elements.
Journal Article•
TL;DR: A hypothesis is presented that the presence of a pseudogene within the CYP2D subfamily transfers detrimental mutations via gene conversions into the CYD2D6 gene, thus accounting for the high frequency of mutations observed in the CYp2D 6 gene in humans.
Abstract: The debrisoquine-4-hydroxylase polymorphism is a genetic variation in oxidative drug metabolism characterized by two phenotypes, the extensive metabolizer (EM) and poor metabolizer (PM). Of the Caucasian populations of Europe and North America, 5%-10% are of the PM phenotype and are unable to metabolize debrisoquine and numerous other drugs. The defect is caused by several mutant alleles of the CYP2D6 gene, two of which are detected in about 70% of PMs. We have constructed a genomic library from lymphocyte DNA of an EM positively identified by pedigree analysis to be homozygous for the normal CYP2D6 allele. The normal CYP2D6 gene was isolated; was completely sequenced, including 1,531 and 3,522 bp of 5' and 3' flanking DNA, respectively; and was found to contain nine exons within 4,378 bp. Two other genes, designated CYP2D7 and CYP2D8P, were also cloned and sequenced. CYP2D8P contains several gene-disrupting insertions, deletions, and termination codons within its exons, indicating that this is a pseudogene. CYP2D7, which is just downstream of CYP2D8P, is apparently normal, except for the presence, in the first exon, of an insertion that disrupts the reading frame. A hypothesis is presented that the presence of a pseudogene within the CYP2D subfamily transfers detrimental mutations via gene conversions into the CYP2D6 gene, thus accounting for the high frequency of mutations observed in the CYP2D6 gene in humans.
TL;DR: A novel, aberrant Rb protein detected in J82 bladder carcinoma cells was not able to form a complex with E1A and was less stable than p105-Rb, which was observed to result from a single point mutation within a splice acceptor sequence in J 82 genomic DNA.
Abstract: The retinoblastoma (Rb) antioncogene encodes a nuclear phosphoprotein, p105-Rb, that forms protein complexes with the adenovirus E1A and SV40 large T oncoproteins. A novel, aberrant Rb protein detected in J82 bladder carcinoma cells was not able to form a complex with E1A and was less stable than p105-Rb. By means of a rapid method for the detection of mutations in Rb mRNA, this defective Rb protein was observed to result from a single point mutation within a splice acceptor sequence in J82 genomic DNA. This mutation eliminates a single exon and 35 amino acids from its encoded protein product.
TL;DR: The sequence of the entire human gene encoding beta-glucocerebrosidase and that of the associated pseudogene is reported to facilitate development of methods for diagnosis of Gaucher disease at the molecular level.
TL;DR: The SCD gene family provides a new model system for the study of differentiation-induced as well as tissue-specific metabolite controlled gene expression in mice from a diet containing unsaturated fatty acids.
TL;DR: The results show that while in normal, adult, human tissues total FN has a widespread distribution, the B-FN isoform is restricted only to synovial cells, to some vessels and areas of the interstitium of the ovary, and to the myometrium, and the results demonstrate that, in vivo, different FN isoforms have a differential distribution.
Abstract: Fibronectin (FN) represents the mixture of a number of structurally different molecules (isoforms) whose make-up varies depending on the FN sources. FN from cultured transformed human cells has a very different isoform composition with respect to its normal counterpart. In fact, SV-40-transformed WI-38VAI3 human fibroblasts produce high levels of a FN isoform (B-FN) which is very poorly expressed in their normal, WI-38, counterpart. We have recently demonstrated that the B-FN isoform derives from a differential splicing pattern of the FN primary transcript which leads, in transformed cells, to a high level expression of the exon ED-B (Zardi, L., B. Carnemolla, A. Siri, T. E. Petersen, G. Paolella, G. Sebastio, and F. E. Baralle. 1987. EMBO (Eur. Mol. Biol. Organ.) J. 6:2337-2342). Here we report on the production and characterization of a monoclonal antibody (BC-1) which recognizes an epitope within the protein sequence coded for by the ED-B exon. This monoclonal antibody makes it possible to carry out immunohistochemical analysis of the distribution of the ED-B-containing FN isoform (B-FN) in human tissues. The results show that while in normal, adult, human tissues total FN has a widespread distribution, the B-FN isoform is restricted only to synovial cells, to some vessels and areas of the interstitium of the ovary, and to the myometrium. On the contrary, the B-FN isoform has a much greater expression in fetal and tumor tissues. These results demonstrate that, in vivo, different FN isoforms have a differential distribution and indicate that the B-FN isoform may play a role in ontogenesis and oncogenetic processes.
TL;DR: Comparison of the exon structure of the tyrosine kinase domain of the INSR with the corresponding regions of the human SRC, ROS, and ERBB2 (NGL) protooncogenes indicates that theExon-intron organization of this region has not been well conserved.
Abstract: The human insulin receptor gene, INSR, and its promoter region have been isolated and characterized. The gene spans greater than 120 kilobase pairs (kbp) and has 22 exons. All introns interrupt protein coding regions of the gene. The 11 exons encoding the alpha subunit of the receptor are dispersed over greater than 90 kbp, whereas the 11 exons encoding the beta subunit are located together in a region of approximately 30 kbp. Three transcriptional initiation sites have been identified and are located 276, 282, and 283 bp upstream of the translation initiation site. In addition, a 247-bp fragment from the promoter region possessing 62.6% of the maximal promoter activity has been identified. This promoter-active fragment lacks a TATA-like sequence but has two possible binding regions for the transcriptional factor Sp1. Comparison of the exon structure of the tyrosine kinase domain of the INSR with the corresponding regions of the human SRC, ROS, and ERBB2 (NGL) protooncogenes indicates that the exon-intron organization of this region has not been well conserved.
TL;DR: A model in which both splicing and nuclear transport of an RNA molecule are coupled to its translation is presented, supporting the idea that UV mutagenesis proceeds through the formation of pyrimidine dimers in mammalian cells.
Abstract: Steady-state dihydrofolate reductase (dhfr) mRNA levels were decreased as a result of nonsense mutations in the dhfr gene. Thirteen DHFR-deficient mutants were isolated after treatment of Chinese hamster ovary cells with UV irradiation. The positions of most point mutations were localized by RNA heteroduplex mapping, the mutated regions were isolated by cloning or by enzymatic amplification, and base changes were determined by DNA sequencing. Two of the mutants suffered large deletions that spanned the entire dhfr gene. The remaining 11 mutations consisted of nine single-base substitutions, one double-base substitution, and one single-base insertion. All of the single-base substitutions took place at the 3' position of a pyrimidine dinucleotide, supporting the idea that UV mutagenesis proceeds through the formation of pyrimidine dimers in mammalian cells. Of the 11 point mutations, 10 resulted in nonsense codons, either directly or by a frameshift, suggesting that the selection method favored a null phenotype. An examination of steady-state RNA levels in cells carrying these mutations and a comparison with similar data from other dhfr mutants (A. M. Carothers, R. W. Steigerwalt, G. Urlaub, L. A. Chasin, and D. Grunberger, J. Mol. Biol., in press) showed that translation termination mutations in any of the internal exons of the gene gave rise to a low-RNA phenotype, whereas missense mutations in these exons or terminations in exon 6 (the final exon) did not affect dhfr mRNA levels. Nuclear run-on experiments showed that transcription of the mutant genes was normal. The stability of mature dhfr mRNA also was not affected, since (i) decay rates were the same in wild-type and mutant cells after inhibition of RNA synthesis with actinomycin D and (ii) intronless minigene versions of cloned wild-type and nonsense mutant genes were expressed equally after stable transfection. We conclude that RNA processing has been affected by these nonsense mutations and present a model in which both splicing and nuclear transport of an RNA molecule are coupled to its translation. Curiously, the low-RNA mutant phenotype was not exhibited after transfer of the mutant genes, suggesting that the transcripts of transfected genes may be processed differently than are those of their endogenous counterparts.
TL;DR: It is found that the first exon of the human dystrophin transcript is different in brain and muscle, indicating that dyStrophin expression could be differentially regulated in these tissues by usage of distinct promoters.
Abstract: DYSTROPHIN is the protein product of the Duchenne/Becker muscular dystrophy locus. It has a relative molecular mass of 427,000 and is encoded by a large RNA transcript processed from more than 65 exons spread over two million base pairs of the human X chromosome1–5. We have used the polymerase chain reaction6 to see whether any of these exons are used alternatively in the different tissues that express dystrophin. As reported for rat dystrophin7, we find that the first exon of the human dystrophin transcript is different in brain and muscle, indicating that dystrophin expression could be differentially regulated in these tissues by usage of distinct promoters. The 3′ end of the dystrophin transcript can be alternatively spliced to create numerous isoforms differing at their carboxy 1 domains; this is the only domain of dystrophin that does not share any similarity with the related cytoskeletal α-actinins3. These alternative transcripts yield dystrophin molecules which may interact with different proteins of the tissues expressing dystrophin.
TL;DR: By using nuclear extracts from HeLa cells, the promoter of human elongation factor-1 alpha gene could stimulate in vitro transcription better than the adenovirus major late promoter.
TL;DR: DNA sequence analysis indicates that the structural gene encoding aromatase cytochrome P-450 (P-450AROM) has a putative TATA (ATAAAA) sequence at -23 base pairs (bp) and putative CAAT binding sequences beginning at -41, -67, and -83 bp and the 5'-flanking region contains sequences similar to consensus sequences of cis-acting elements defined as regulators of aromatases gene expression.
TL;DR: Alternative splicing of a 36 base pair exon, exon 11, generates hINSR transcripts encoding receptor isoforms which differ in sequence at the C-terminal end of the insulin-binding alpha-subunit.
TL;DR: Four major tau protein isoforms isolated from bovine brain were identified by comparison with translation products of cDNA constructs and the use of antisera raised against synthetic peptides to provide reagents and a basis for analyzing potentially altered forms of tau proteins in brains of patients with Alzheimer's disease.
Abstract: Tau, a major class of microtubule-associated proteins, consists of a family of proteins that are heterogeneous in molecular weight. The presence of internal deletions in previously described cDNA clones for murine and bovine tau suggested that alternative splicing of transcripts could account for the protein size heterogeneity. Analysis of the exon-intron structure of the bovine tau gene provided sequence information necessary to detect new variants of tau transcripts by in vitro amplification techniques. The variant transcripts found corresponded to mRNA species missing one or more exons, which suggested that by skipping various exons during mRNA splicing, a family of proteins is generated. Four major tau protein isoforms isolated from bovine brain were identified by comparison with translation products of cDNA constructs and the use of antisera raised against synthetic peptides. These studies provide reagents and a basis for analyzing potentially altered forms of tau proteins in brains of patients with Alzheimer's disease.
TL;DR: Although the functional significance of alternative splicing of the insulin receptor mRNA is unknown, differential expression of these two receptor mRNAs may provide a structural basis for previously observed tissue-specific differences in insulin binding and action.
Abstract: Two previously reported insulin receptor cDNA sequences differ by 36 base pairs (bp) in the distal alpha-subunit, suggesting that alternative mRNA splicing within the coding region may occur (two insulin receptor isoforms). We developed a quantitative modification of the polymerase chain reaction technique in order to detect and characterize differential mRNA splicing at this site within the distal alpha-subunit. Using RNA derived from a variety of human cell types, we detected two polymerase chain reaction-amplified cDNA species reflecting the presence or absence of the above 36 nucleotides. Identity of the two cDNA species was confirmed by Southern blots, the use of a BANI restriction site present only in the 36 base pair segment and dideoxy sequencing. The relative expression of the two mRNA forms varied markedly in a tissue-specific manner. Buffy coat leukocytes and Epstein-Barr virus-transformed lymphocytes express only the shorter mRNA. Placenta expresses both species equally; muscle, isolated adipocytes and cultured fibroblasts express somewhat more of the longer mRNA (relative ratios of mRNA abundance of 1.51, 3.18, and 2.77, respectively); liver expresses mostly the longer mRNA (relative ratio of 9.8). In RNA derived from cultured and fresh cells from patients with several states of insulin resistance, the relative expression of the two mRNA species was similar to results obtained with comparable normal tissues. Although the functional significance of alternative splicing of the insulin receptor mRNA is unknown, differential expression of these two receptor mRNAs may provide a structural basis for previously observed tissue-specific differences in insulin binding and action.
TL;DR: The gene conferring expression of tum- antigen P91A contains 12 exons, encoding a 60 kd protein lacking a typical N-terminal signal sequence, which creates a strong aggretope enabling the peptide to bind the H-2 Ld molecule.
TL;DR: The arm gene produces two types of very abundant 3.2-kb transcripts that differ only in their first exons as mentioned in this paper, and these RNAs appear to be formed by independent transcriptional initiation but have similar patterns of expression throughout development.
Abstract: During Drosophila embryogenesis, the segment polarity genes are required for the formation of specific pattern domains within each segment. Mutations in the armadillo (arm) gene primarily affect the posterior part of the segment and lead to the production of anterior structures within this region. To examine the molecular basis for these effects, we have cloned the arm region and identified the gene by germ-line transformation. The arm gene produces two types of very abundant 3.2-kb transcripts that differ only in their first exons. These RNAs appear to be formed by independent transcriptional initiation but have similar patterns of expression throughout development. Both arm transcripts are present in virtually all of the cell types contained in embryos, third-instar larvae, and adult ovaries, suggesting that arm may be required in all cells. In addition, the arm transcripts are uniformly distributed in embryonic segments, so the regional pattern defects associated with its embryonic phenotype may result from interactions between arm and other localized factors. Both arm RNAs encode the same 91-kD polypeptide. This protein has no probable secretory or membrane-spanning regions and contains a series of novel internal repeats that are conserved in sequence, length, and spacing. Considering these results and previous genetic observations, we discuss potential roles for the arm gene in pattern formation processes.
TL;DR: The results indicate that the splicing of intron 2 in the rabbit beta-globin gene occurs ahead of polyadenylation and have important implications for termination of transcription.
Abstract: We constructed and analyzed a synthetic poly(A) (SPA) site that was based on the highly efficient poly(A) signal of the rabbit beta-globin gene. By use of the SPA, we demonstrate that the minimum sequences required for efficient polyadenylation are the AATAAA sequence and a GT/T-rich sequence with the correct spacing of 22-23 nucleotides between them. When placed downstream of the poly(A) site of the human alpha 2-globin gene, the SPA is used exclusively. We predict that the SPA, with its more extensive GT/T-rich sequence, is a more efficient poly(A) site than alpha-globin. Also, we compared the use of the SPA when it is placed either in the exon 3 or intron 2 of the rabbit beta-globin gene. When in the exonic position, SPA is used 10-fold more than the regular poly(A) site of rabbit beta-globin. In contrast, when it is in the intronic location, no detectable use of SPA is observed; however, the deletion of the donor site of intron 2 reactivates the intronic positioned SPA. These results indicate that the splicing of intron 2 in the rabbit beta-globin gene occurs ahead of polyadenylation and have important implications for termination of transcription. Polyadenylation, although required for termination of transcription, is not sufficient; therefore, additional termination signals for RNA polymerase II must exist.
TL;DR: Sequence comparison shows that, while R2 is most related to CD1a, ‐b and ‐c, albeit to a somewhat lower degree than the latter are to themselves, R3 is more homologous to mouse than to human CD1, suggesting the existence of two functional classes within the CD1 gene family.
Abstract: Herein, we report the DNA sequence of two human CD1 genes, R2 and R3, distinct from those encoding the CD1a, -b and -c antigens. Both genes appear to have an exon/intron structure analogous to the previously analyzed CD1 genes and to be functional on the basis of their sequence. Analysis of the variability patterns, potential intramolecular interactions and predicted secondary structure profile on an alignment of all known CD1 α chains suggest some shared structural features with major histocompatibility complex class I molecules in the α1 domains but substantial differences in the α2 domains. Sequence comparison shows that, while R2 is most related to CD1a, -b and -c, albeit to a somewhat lower degree than the latter are to themselves, R3 is more homologous to mouse than to human CD1, suggesting the existence of two functional classes within the CD1 gene family. We propose to retain the non-committal R2 and R3 names until the putative antigens have been identified and their tissue distribution has been established.
TL;DR: The altered HIV-1 mRNA profile induced by the antisense phosphorothioate oligomer suggests that the mechanism for the inhibition of viral expression is due to an interference with the regulatory gene, rev, by translation arrest.
Abstract: In this report, we demonstrate the sequence-specific suppression of viral expression in T cells chronically infected with human immunodeficiency virus 1 (HIV-1), using antisense phosphorothioate oligodeoxynucleotides. As a target for antisense intervention, we used the HIV-1 gene rev, which is essential for viral replication and regulates the expression of virion proteins, in part, by affecting the splicing of the viral mRNA. A phosphorothioate oligomer complementary to the initiation sequence of HIV-1 rev had a significant and selective inhibitory effect on the production of several viral proteins in chronically HIV-1-infected T cells and drastically reduced the unspliced (genomic) viral mRNA transcripts, with relative sparing of smaller (spliced) transcripts. By contrast, the antisense sequence with unmodified normal phosphodiester linkages as well as phosphorothioate oligomers containing sense, random, homopolymeric sequences, or antisense sequence with N3-methylthymidine residues did not have an inhibitory effect on viral expression. Thus, sequence specificity and nuclease resistance were critical for the anti-viral-gene regulatory effect of the antisense molecules. The altered HIV-1 mRNA profile induced by the antisense phosphorothioate oligomer suggests that the mechanism for the inhibition of viral expression is due to an interference with the regulatory gene, rev, by translation arrest.
TL;DR: Analysis of constructs containing native and mutated ISREs suggests that this motif is essential for the response of 9-27 toIFN-gamma as well as IFN-alpha, and the9-27 (GGAAATAGAAACT) and 6-16 (GGGAAAATGAAACT), which can each confer a response to both types of IFN when placed on the 5' side of a marker gene.
Abstract: Genomic and cDNA clones corresponding to 9-27, a member of the human 1-8 gene family highly inducible by alpha- and gamma-interferons (IFNs), have been isolated and characterized. A 1.7-kilobase genomic clone contains a complete functional gene with two exons, encoding a 125-amino acid polypeptide of unknown function. The 5' flanking region of the gene contains a 13-base-pair IFN-stimulable response element (ISRE), homologous to the ISREs of the 6-16, ISG 15, and ISG 54 genes, which are predominantly inducible by IFN-alpha, beta. Analysis of constructs containing native and mutated ISREs suggests that this motif is essential for the response of 9-27 to IFN-gamma as well as IFN-alpha. Furthermore, the 9-27 (GGAAATAGAAACT) and 6-16 (GGGAAAATGAAACT) ISREs can each confer a response to both types of IFN when placed on the 5' side of a marker gene. Since the 6-16 gene does not normally respond to IFN-gamma, the context of the ISRE must determine the specificity of the response.