Abstract
Many cytokine mRNAs exhibit a conserved, AU-rich motif in the 3'-untranslated region (UTR) of the molecule. Such sequence elements have been implicated in the regulation of mRNA turnover and as potential translational regulators. We report on the identification of a 3 base pair insertion which disrupts the AU motif of the TNF-alpha gene in the NZW, B10.KPA44, SM/J and Mus spretus mice and an insertion of an 8 base pair sequence into the 3' AU motif of the IL-10 gene in the Mus Spretus mouse. The mutation in the AU motif of the TNF-alpha gene correlates with reduced production of this cytokine by peritoneal macrophages from these mouse strains.
MeSH Terms
Adenine
Animals
Base Composition
Base Sequence
Conserved Sequence
DNA/genetics,isolation & purification
Genome
Liver/metabolism
Macrophages/metabolism
Mice/genetics
Mice, Inbred Strains/genetics
Molecular Sequence Data
Muridae/genetics
Polymerase Chain Reaction/methods
Protein Biosynthesis
RNA, Messenger/genetics,metabolism
Regulatory Sequences, Nucleic Acid
Spleen/metabolism
Tumor Necrosis Factor-alpha/biosynthesis,genetics
Uracil
Chemicals
RNA, Messenger
Tumor Necrosis Factor-alpha
Uracil
DNA
Adenine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Jacob C O
Institute of Immunology and Biological Sciences, Syntex Research, Palo Alto, CA 94304.
Tashman N B
References (21)
21 references, click to expand
-
Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor.
Proc Natl Acad Sci U S A. 1985 Sep;82(18):6060-4
PMID: 3898078
-
Structure of the mouse IL-10 gene and chromosomal localization of the mouse and human genes.
J Immunol. 1992 Jun 1;148(11):3618-23
PMID: 1350294
-
Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators.
Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670-4
PMID: 2419912
-
Evolutionary relationships in the genus Mus.
Curr Top Microbiol Immunol. 1986;127:19-34
PMID: 3731841
-
A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation.
Cell. 1986 Aug 29;46(5):659-67
PMID: 3488815
-
Genes for the tumor necrosis factors alpha and beta are linked to the human major histocompatibility complex.
Proc Natl Acad Sci U S A. 1986 Nov;83(22):8699-702
PMID: 3464978
-
Tumour necrosis factor and lymphotoxin genes map close to H-2D in the mouse major histocompatibility complex.
Nature. 1987 Jan 15-21;325(6101):265-7
PMID: 3027565
-
The murine interleukin 1 beta gene: structure and evolution.
Nucleic Acids Res. 1986 Dec 22;14(24):9955-63
PMID: 3492706
-
The 3' untranslated region of the human interferon-beta mRNA has an inhibitory effect on translation.
Proc Natl Acad Sci U S A. 1987 Sep;84(17):6030-4
PMID: 3476924
-
Nucleotide sequence of the murine TNF locus, including the TNF-alpha (tumor necrosis factor) and TNF-beta (lymphotoxin) genes.
Nucleic Acids Res. 1987 Nov 11;15(21):9083-4
PMID: 3684584
-
Tumour necrosis factor-alpha in murine autoimmune 'lupus' nephritis.
Nature. 1988 Jan 28;331(6154):356-8
PMID: 2893286
-
Genomic structure of the murine IL-6 gene. High degree conservation of potential regulatory sequences between mouse and human.
J Immunol. 1988 Dec 1;141(11):3875-81
PMID: 3263439
-
Translational blockade imposed by cytokine-derived UA-rich sequences.
Science. 1989 Aug 25;245(4920):852-5
PMID: 2672333
-
Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages.
J Exp Med. 1990 Jan 1;171(1):35-47
PMID: 2104921
-
Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus.
Proc Natl Acad Sci U S A. 1990 Feb;87(3):1233-7
PMID: 2105500
-
Endotoxin-responsive sequences control cachectin/tumor necrosis factor biosynthesis at the translational level.
J Exp Med. 1990 Feb 1;171(2):465-75
PMID: 2303781
-
The generation and maintenance of MHC class II gene polymorphism in rodents.
Immunol Rev. 1990 Feb;113:207-26
PMID: 2180807
-
Interactive effects of the tumor necrosis factor promoter and 3'-untranslated regions.
J Immunol. 1991 Mar 15;146(6):1843-8
PMID: 1848573
-
Immune hormones (cytokines); pathogenic role in autoimmune rheumatic and endocrine diseases.
Autoimmunity. 1989;2(2):177-89
PMID: 2491601
-
Tumor necrosis factor alpha in murine systemic lupus erythematosus disease models: implications for genetic predisposition and immune regulation.
Cytokine. 1991 Nov;3(6):551-61
PMID: 1686413
-
Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization.
Nucleic Acids Res. 1985 Sep 11;13(17):6361-73
PMID: 2995927