The effect of the fungal metabolite radicicol analog A on mRNA degradation

The AU-rich element (ARE) is a stability determinant found in the 3′ UTR of a number of short-lived mRNAs. The best characterized ARE is the Shaw–Kamen (SK) box or AUUUA motif. Previously, a fungal metabolite, radicicol analog A (RAA), was shown to destabilize SK box-containing mRNAs based on 16 mRNAs examined [T. Kastelic et al., Cytokine 8 (1996) 751–761]. Using serial analysis of gene expression (SAGE) to examine the global effect of RAA on mRNA expression in interferon-γ/lipopolysaccharide-stimulated THP-1 human monocytes, we observed that the expression level of greater than 99% of the SAGE tags was unchanged by RAA treatment and only 34 of the 17,608 unique tags annotated were reduced (p ≤ 0.0001). RAA destabilized approximately half of the down-regulated transcripts. Whereas all the destabilized mRNAs possessed at least one SK box, for transcripts not destabilized but nonetheless down-regulated, RAA appears to function by a SK box-independent mechanism not currently understood.