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-gamma/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< or =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.
Mak
Isabella W Y
IW
BC Cancer Research Centre, BC Cancer Agency, Vancouver, BC, Canada.
Liu
Lin
L
Ling
Victor
V
Kastelic
Tania
T
D020413:3' Untranslated Regions; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005658:Fungi / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020413:3' Untranslated Regions; D017931:DNA Primers; D008070:Lipopolysaccharides; D018942:Macrolides; D012333:RNA, Messenger; D007371:Interferon-gamma; C035359:monorden