The role of AUF1 in regulated mRNA decay.

Messenger ribonucleic acid (mRNA) turnover is a major control point in gene expression. In mammals, many mRNAs encoding inflammatory cytokines, oncoproteins, and G-protein-coupled receptors are destabilized by the presence of AU-rich elements (AREs) in their 3'-untranslated regions. Association of ARE-binding proteins (AUBPs) with these mRNAs promotes rapid mRNA degradation.

Chaperone Hsp27 modulates AUF1 proteolysis and AU-rich element-mediated mRNA degradation.

AUF1 is an AU-rich element (ARE)-binding protein that recruits translation initiation factors, molecular chaperones, and mRNA degradation enzymes to the ARE for mRNA destruction. We recently found chaperone Hsp27 to be an AUF1-associated ARE-binding protein required for tumor necrosis factor alpha (TNF-α) mRNA degradation in monocytes. Hsp27 is a multifunctional protein that participates in ubiquitination of proteins for their degradation by proteasomes.

Chaperone Hsp27, a novel subunit of AUF1 protein complexes, functions in AU-rich element-mediated mRNA decay.

Controlled, transient cytokine production by monocytes depends heavily upon rapid mRNA degradation, conferred by 3' untranslated region-localized AU-rich elements (AREs) that associate with RNA-binding proteins. The ARE-binding protein AUF1 forms a complex with cap-dependent translation initiation factors and heat shock proteins to attract the mRNA degradation machinery. We refer to this protein assembly as the AUF1- and signal transduction-regulated complex, ASTRC.