The role of AUF1 in regulated mRNA decay.

ABSTRACT

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. ARE/poly(U)-binding/degradation factor 1 (AUF1), one of the best-characterized AUBPs, binds to many ARE-mRNAs and assembles other factors necessary to recruit the mRNA degradation machinery. These factors include translation initiation factor eIF4G, chaperones hsp27 and hsp70, heat-shock cognate protein hsc70, lactate dehydrogenase, poly(A)-binding protein, and other unidentified proteins. Numerous signaling pathways alter the composition of this AUF1 complex of proteins to effect changes in ARE-mRNA degradation rates. This review briefly describes the roles of mRNA decay in gene expression in general and ARE-mediated decay (AMD) in particular, with a focus on AUF1 and the different modes of regulation that govern AUF1 involvement in AMD.