Disruption in the AU motif of the mouse TNF-alpha 3' UTR correlates with reduced TNF production by macrophages in vitro.
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.
Jacob
C O
CO
Institute of Immunology and Biological Sciences, Syntex Research, Palo Alto, CA 94304.
Tashman
N B
NB
D000225:Adenine; D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D016678:Genome; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice / Q000235:genetics*; D008815:Mice, Inbred Strains / Q000235:genetics; D008969:Molecular Sequence Data; D009115:Muridae / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D013154:Spleen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*; D014498:Uracil
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014498:Uracil; D004247:DNA; D000225:Adenine