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. Copyright © 2010 John Wiley & Sons, Ltd. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability