SummaryDifferent vectors were constructed that expressed the human interferon-0 (IFN-0) mRNA constitutively and contained various deletions in the 3' untranslated region (UTR). AU-rich sequences in the 3' UTR were specifically deleted in two vectors . Cell lines secreting human IFN-O were established by transfecting murine L929 cells with the vectors . These cells showed similar levels of IFN-,Q mRNA and secreted comparable amounts of IFN-,13, indicating that the deletion of AU-rich sequences had no effect on the stability and little effect on the efficiency of translation ofthis mRNA. The synthetic glucocorticoid dexamethasone was previously shown to increase the turnover of IFN-O mRNA. This activity of dexamethasone was clearly observed only in cells expressing IFN-O mRNA with AU-rich sequences in the 3' UTR . The increased turnover of this mRNA occurred in the presence of cycloheximide; therefore, it did not require synthesis of new proteins. These findings suggest that glucocorticoids may activate a ribonuclease that degrades mRNAs containing AU-rich sequences in the 3' UTR.G lucocorticoids regulate gene expression in different ways.When these hormones bind to cytoplasmic receptors, glucocorticoid-receptor complexes translocate into the nucleus where they bind to target DNA sequences with high affinity (see reference 1 for a review) . This binding is a primary response that does not require protein synthesis and either stimulates or represses gene transcription (1), as it has been shown for ot-fetoprotein (2) and proopiomelanocortin (3) . Glucocorticoids can also modulate gene expression posttranscriptionally. For example, the stability offibronectin (4) and human growth hormone mRNA is enhanced by glucocorticoid treatment (5) ; concomitantly, the length of the poly(A) tail of this mRNA is increased (6) . Moreover, the mRNA for phosphoenolpyruvate carboxykinase contains a a glucocorticoid-responsive stabilizing element (7) . In contrast, the glucocorticoids inhibit the synthesis of certain cytokines and ofother proteins post-transcriptionally. Treatment with the synthetic glucocorticoid dexamethasone (DEX)' has been shown to destabilize the mRNA for IIAO (8), type 1 procollagen (9) and 3-hydroxy-3-methylglutarylcoenzyme A reductase (10). In addition, DEX inhibits the 'Abbreviations used in this payer: AU elements, AU-rich sequences in the 3' untranslated region; DEX, dexamethasone; GAPDH, glyceraldehyde 3-phosphate dehydrogenase ; GM-CSF, granulocyte-monocyte colonystimulating factor; TE, 10 mm Tris-HO, pH 7 .5, 1 mM EDTA; tk, herpes simplex virus thymidine kinase gene ; UTR, untranslated region . synthesis of T cell growth factor and the accumulation of IFN -,y mRNA in phytohemoagglutinin-stimulated lymphocytes (11), and decreases the level of nerve growth factor mRNA in L929 cells (12).Treatment with glucocorticoids inhibits production of IFN and increases the lethality of Coxsackie virus in infected mice (13)(14) . DEX decreases IFN production (15) and increases the turnover of IFN-O mRNA in human fibrobl...

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