A review of methods to monitor the modulation of mRNA stability: a novel approach to drug discovery and therapeutic intervention.

Posttranscriptional regulation of gene expression is an elaborate and intricate process, constituting an important mechanism for the control of protein expression. During its existence, mRNA is escorted by proteins and other RNAs, which control the maturation, transportation, localization, translational efficiency, and ultimately its degradation. Without changes at the transcription level, mRNA steady-state levels can vary dramatically by just small changes in mRNA stability.

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.

Effects of soluble interleukin-1 type II receptor on rabbit antigen-induced arthritis: clinical, biochemical and histological assessment.

Objectives: To investigate the effects of soluble interleukin-1 (IL-1) type II receptor (sIL-1RII) on a number of clinical, biochemical and histological parameters in rabbit antigen-induced arthritis.

Methods: Arthritis was induced by intra-articular injection of methylated bovine serum albumin (mBSA) into rabbits pre-sensitized to the same antigen. An initial i.

Increased mature interleukin-1beta (IL-1beta) secretion from THP-1 cells induced by nigericin is a result of activation of p45 IL-1beta-converting enzyme processing.

Perregaux and Gabel (Perregaux, D., and Gabel, C. A.

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.