title: The essential role of the UA-rich sequence in endotoxin-induced cachectin/TNF synthesis.
abstract: Using a series of reporter constructs in which a CAT coding sequence is constitutively transcribed under the influence of the SV40 late promoter but followed by varying portions of the 3'-untranslanted region of TNF, we have shown that the UA-rich element, present in the distal third of the 3'-unstranslated region of TNF, is absolutely required for translational activation of TNF synthesis. Replacement of the UA-rich element by an unrelated sequence of similar length completely abolishes the response. However, the context within which the UA-rich element is presented also appears to be essential, since replacement of flanking portions of 3'-untranslated sequence also blocks the response to LPS. These findings suggest that the primary role of the UA-rich element may consist in its ability to mediate translational activation in response to specific inducing signals.
authors.affiliation: Department of Internal Medicine, U.T. Southwestern Medical Center, Dallas 75235-9050.
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.forename: B
authors.initials: B
authors.lastname: Beutler
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004731:Endotoxins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D013539:Simian virus 40 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004731:Endotoxins; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha