The Essential Role of the UA-rich Sequence in Endotoxin-induced Cachectin/TNF Synthesis

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.