Home LiteratureArticle Details
PMID: 2416561 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 4 ·No. 9 ·1985-09-00 ·Pages 2249-56

Benech P, Mory Y, Revel M, Chebath J

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.

MeSH Terms
2',5'-Oligoadenylate Synthetase/biosynthesis,genetics Amino Acid Sequence Base Sequence Burkitt Lymphoma Cell Line Cloning, Molecular DNA/isolation & purification DNA Restriction Enzymes Enzyme Induction Genes Humans Interferons/pharmacology Male Nucleic Acid Hybridization Poly A/genetics RNA/genetics RNA, Messenger Skin/enzymology Transcription, Genetic
Chemicals
RNA, Messenger Poly A RNA DNA Interferons 2',5'-Oligoadenylate Synthetase DNA Restriction Enzymes
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Benech P
Mory Y
Revel M
Chebath J
References (61)
61 references, click to expand
  1. Differential regulation of HLA-DR mRNAs and cell surface antigens by interferon.
    EMBO J. 1983;2(9):1585-9 PMID: 11892816
  2. alpha-Interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences.
    Nature. 1985 Apr 18-24;314(6012):637-9 PMID: 3990797
  3. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I.
    J Mol Biol. 1977 Jun 15;113(1):237-51 PMID: 881736
  4. Nature of inhibitor of cell-free protein synthesis formed in response to interferon and double-stranded RNA.
    Nature. 1977 Aug 11;268(5620):540-2 PMID: 196217
  5. pppA2'p5'A2'p5'A: an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells.
    Proc Natl Acad Sci U S A. 1978 Jan;75(1):256-60 PMID: 272640
  6. The isolation of structural genes from libraries of eucaryotic DNA.
    Cell. 1978 Oct;15(2):687-701 PMID: 719759
  7. Interferon action: isolation of nuclease F, a translation inhibitor activated by interferon-induced (2'-5') oligo-isoadenylate.
    FEBS Lett. 1978 Nov 15;95(2):257-64 PMID: 720619
  8. Isolation of two interferon-induced translational inhibitors: a protein kinase and an oligo-isoadenylate synthetase.
    Proc Natl Acad Sci U S A. 1978 Oct;75(10):4734-8 PMID: 283387
  9. 2-5A synthetase: assay, distribution and variation with growth or hormone status.
    Nature. 1979 Mar 29;278(5703):471-3 PMID: 450053
  10. Transformation of mammalian cells with genes from procaryotes and eucaryotes.
    Cell. 1979 Apr;16(4):777-85 PMID: 222468
  11. Structural requirements of double-stranded RNA for the activation of 2',5'-oligo(A) polymerase and protein kinase of interferon-treated HeLa cells.
    J Biol Chem. 1979 Oct 25;254(20):10180-3 PMID: 489592
  12. Interferon, double-stranded RNA, and RNA degradation. Isolation of homogeneous pppA(2'p5'A)n-1 synthetase from Ehrlich ascites tumor cells.
    J Biol Chem. 1980 May 10;255(9):3813-6 PMID: 6154703
  13. Sequencing end-labeled DNA with base-specific chemical cleavages.
    Methods Enzymol. 1980;65(1):499-560 PMID: 6246368
  14. An interferon-induced cellular enzyme is incorporated into virions.
    Nature. 1980 Sep 4;287(5777):68-70 PMID: 6157996
  15. Synthesis of (2'-5')(A)n from ATP. Characteristics of the reaction catalyzed by (2'-5')(A)n synthetase purified from mouse Ehrlich ascites tumor cells treated with interferon.
    J Biol Chem. 1980 Oct 25;255(20):9807-13 PMID: 6159349
  16. Increased levels of (2'-5')oligo(A) polymerase activity in human lymphoblastoid cells treated with glucocorticoids.
    Proc Natl Acad Sci U S A. 1980 Nov;77(11):6506-10 PMID: 6161367
  17. Interferon-induced (2'-5')oligoadenylate synthetase: adsorpton to and assay on adenosine 2',5'-diphosphate-sepharose.
    Biochemistry. 1980 Nov 25;19(24):5580-5 PMID: 6161641
  18. Role of interferon-induced enzymes in the antiviral and antimitogenic effects of interferon.
    Ann N Y Acad Sci. 1980;350:459-72 PMID: 6165297
  19. Induction, purification, and properties of 2'5' oligoadenylate synthetase.
    Ann N Y Acad Sci. 1980;350:486-96 PMID: 6165299
  20. Primary structure, gene organization and polypeptide expression of poliovirus RNA.
    Nature. 1981 Jun 18;291(5816):547-53 PMID: 6264310
  21. Interferons, double-stranded RNA, and RNA degradation. Isolation and characterization of homogeneous human (2'-5')(a)n synthetase.
    J Biol Chem. 1981 Sep 10;256(17):9324-8 PMID: 6167587
  22. Organization and expression of eucaryotic split genes coding for proteins.
    Annu Rev Biochem. 1981;50:349-83 PMID: 6791577
  23. The 2'5' oligoadenylate synthetase has a multifunctional 2'5' nucleotidyl-transferase activity.
    Biochem Biophys Res Commun. 1981 May 29;100(2):847-56 PMID: 6268077
  24. A mouse cell line, which is unprotected by interferon against lytic virus infection, lacks ribonuclease F activity.
    Eur J Biochem. 1981 Aug;118(1):9-15 PMID: 6169526
  25. Nucleotide sequence of the chromosomal gene for human fibroblast (beta 1) interferon and of the flanking regions.
    Gene. 1981 Aug;14(3):137-43 PMID: 6169589
  26. Synthesis of human interferon beta 1 in Escherichia coli infected by a lambda phage recombinant containing a human genomic fragment.
    Eur J Biochem. 1981 Nov;120(1):197-202 PMID: 6171427
  27. Antimitogenic effects of interferon and (2'-5')-oligoadenylate in synchronized 3T3 fibroblasts.
    FEBS Lett. 1981 Nov 16;134(2):212-6 PMID: 6171460
  28. Presence of 2',5'-oligo(A) and of enzymes that synthesize, bind, and degrade 2',5'-oligo(A) in HeLa cell nuclei.
    J Biol Chem. 1982 Feb 25;257(4):1602-5 PMID: 6173380
  29. Interferon-induced enzymes: microassays and their applications: purification and assay of (2'-5')-oligoadenylate synthetase and assay of 2'-phosphodiesterase.
    Methods Enzymol. 1981;79(Pt B):149-61 PMID: 6173659
  30. A convenient and adaptable package of DNA sequence analysis programs for microcomputers.
    Nucleic Acids Res. 1982 Jan 11;10(1):51-9 PMID: 6278412
  31. Analysis of interferon mRNA in human fibroblast cells induced to produce interferon.
    Proc Natl Acad Sci U S A. 1981 Dec;78(12):7426-30 PMID: 6174973
  32. Exon/intron organization and complete nucleotide sequence of an HLA gene.
    Proc Natl Acad Sci U S A. 1982 Feb;79(3):893-7 PMID: 6461010
  33. 3' end structure of the human (2'-5') oligo A synthetase gene: prediction of two distinct proteins with cell type-specific expression.
    Nucleic Acids Res. 1985 Feb 25;13(4):1267-81 PMID: 2860635
  34. Analogue inhibitor of 2-5A action: effect on the interferon-mediated inhibition of encephalomyocarditis virus replication.
    EMBO J. 1985 Feb;4(2):431-6 PMID: 2410258
  35. Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts and lymphoblastoid cells.
    Proc Natl Acad Sci U S A. 1982 May;79(10):3082-6 PMID: 6179076
  36. A simple method for displaying the hydropathic character of a protein.
    J Mol Biol. 1982 May 5;157(1):105-32 PMID: 7108955
  37. Heterogeneous nuclear RNA promotes synthesis of (2',5')oligoadenylate and is cleaved by the (2',5')oligoadenylate-activated endoribonuclease.
    Mol Cell Biol. 1982 Feb;2(2):154-60 PMID: 6180300
  38. Biochemistry of interferons and their actions.
    Annu Rev Biochem. 1982;51:251-82 PMID: 6180680
  39. Human metallothionein genes--primary structure of the metallothionein-II gene and a related processed gene.
    Nature. 1982 Oct 28;299(5886):797-802 PMID: 7133118
  40. A high speed, high capacity homology matrix: zooming through SV40 and polyoma.
    Nucleic Acids Res. 1982 Aug 11;10(15):4765-82 PMID: 6290988
  41. A unique set of polypeptides is induced by gamma interferon in addition to those induced in common with alpha and beta interferons.
    Nature. 1983 Feb 3;301(5899):437-9 PMID: 6218412
  42. Variation of (2'-5')oligo(adenylate) synthetase activity during rat-liver regeneration.
    Eur J Biochem. 1983 Feb 1;130(2):269-73 PMID: 6825692
  43. Interferon-induced 56,000 Mr protein and its mRNA in human cells: molecular cloning and partial sequence of the cDNA.
    Nucleic Acids Res. 1983 Mar 11;11(5):1213-26 PMID: 6186990
  44. Human beta-globin pre-mRNA synthesized in vitro is accurately spliced in Xenopus oocyte nuclei.
    Cell. 1983 Mar;32(3):681-94 PMID: 6550524
  45. Growth regulation of melanoma cells by interferon and (2'-5')oligoadenylate synthetase.
    Mol Cell Biol. 1983 May;3(5):780-6 PMID: 6865941
  46. Molecular cloning and sequence of partial cDNA for interferon-induced (2'-5')oligo(A) synthetase mRNA from human cells.
    Proc Natl Acad Sci U S A. 1983 Aug;80(16):4904-8 PMID: 6348777
  47. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene.
    Cell. 1983 Oct;34(3):865-79 PMID: 6313211
  48. Isolation and characterization of an interferon-resistant cell line deficient in the induction of (2'-5')oligoadenylate synthetase activity.
    Mol Cell Biol. 1983 Oct;3(10):1759-65 PMID: 6646121
  49. Point mutations close to the AUG initiator codon affect the efficiency of translation of rat preproinsulin in vivo.
    Nature. 1984 Mar 15-21;308(5956):241-6 PMID: 6700727
  50. Organization of the transcriptional unit of a human class II histocompatibility antigen: HLA-DR heavy chain.
    Nucleic Acids Res. 1983 Dec 20;11(24):8663-75 PMID: 6324094
  51. Immunological evidence for the in vivo occurrence of (2'-5')adenylyladenosine oligonucleotides in eukaryotes and prokaryotes.
    Proc Natl Acad Sci U S A. 1984 Apr;81(8):2322-6 PMID: 6425831
  52. Complete nucleotide sequence of a functional class I HLA gene, HLA-A3: implications for the evolution of HLA genes.
    EMBO J. 1984 Apr;3(4):887-94 PMID: 6609814
  53. Mechanisms of antiviral action of interferon.
    Interferon. 1983;5:23-42 PMID: 6202642
  54. Autogenous production of interferon-beta switches on HLA genes during differentiation of histiocytic lymphoma U937 cells.
    EMBO J. 1984 May;3(5):969-73 PMID: 6376119
  55. Chromosomal location of mouse gene 202 which is induced by interferons and specifies a 56.5 kD protein.
    J Interferon Res. 1984 Spring;4(2):295-300 PMID: 6205102
  56. Interferon action: two (2'-5')(A)n synthetases specified by distinct mRNAs in Ehrlich ascites tumor cells treated with interferon.
    Cell. 1983 May;33(1):95-102 PMID: 6205763
  57. A human IFN-beta 1 gene deleted of promoter sequences upstream from the TATA box is controlled post-transcriptionally by dsRNA.
    Nucleic Acids Res. 1984 Sep 25;12(18):6979-93 PMID: 6091048
  58. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells.
    Cell. 1984 Oct;38(3):745-55 PMID: 6548414
  59. The RNA lariat: a new ring to the splicing of mRNA precursors.
    Cell. 1984 Dec;39(3 Pt 2):423-5 PMID: 6568879
  60. Major deletions in the gene encoding the p53 tumor antigen cause lack of p53 expression in HL-60 cells.
    Proc Natl Acad Sci U S A. 1985 Feb;82(3):790-4 PMID: 2858093
  61. The beta2-microglobulin mRNA in human Daudi cells has a mutated initiation codon but is still inducible by interferon.
    EMBO J. 1983;2(2):239-43 PMID: 11894933
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1985-09-00
Pages
2249-56
Language
English
Region
England
NLM ID
8208664
PMCID
PMC554493
Subset
IM
Databases
GENBANK
K00006, M11803, M11804, M11805, M11806, M11807, M11808, M11809, M11810, X02874, X02875
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2