Induction of rapid IL-1 beta mRNA degradation in THP-1 cells mediated through the Au-rich region in the 3'UTR by a radicicol analogue

A radicicol analogue (analogue A) was found to inhibit interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF-alpha) secretion from THP-1 cells, If added to cells activated by interferon gamma and lipopolysaccharide, radicicol analogue A not only inhibited the secretion of IL-1 beta but also induced an extremely rapid degradation of IL-1 beta, IL-6 and TNF-alpha mRNA to undetectable levels within 5-8 h. This degradation is independent of translation and of the signal inducing transcription, The common feature of these genes is the inclusion of one or more copies of the mRNA-instability sequence, AUUUA, in the 3' untranslated region, Indeed, no destabilizing effect of radicicol analogue A could be observed on mRNA derived from the expression of an IL-1 beta construct lacking the AUUUA motifs of the 3'UTR. The effect of radicicol analogue A on protein/mRNA interaction and on post-translational modifications of cytoplasmic proteins is described, This class of compound constitutes a valuable tool for the further elucidation of the mechanism of mRNA degradation of cytokines and proto-oncogenes. (C) 1996 Academic Press Limited