Induction of Rapid IL-beta mRNA Degradation in THP-1 Cells Mediated Through the AU-Rich Region in the 3'UTR by a Radicicol Analogue

Author： Kastelic T. Schnyder J. Leutwiler A. Traber R. Streit B. Niggli H. MacKenzie A. Cheneval D.

Publisher： Academic Press

ISSN： 1043-4666

Source： Cytokine, Vol.8, Iss.10, 1996-10, pp. : 751-761

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Abstract

A radicicol analogue (analogue A) was found to inhibit interleukin 1 beta (IL-1beta) 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-1beta but also induced an extremely rapid degradation of IL-1beta, 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-1beta 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.