Regulation of mRNA Stability by AUF1
A+U-rich elements (AREs) are potent cis-acting determinants of rapid cytoplasmic mRNA turnover in mammalian cells. Regulation of mRNA decay rates by these sequences is mediated by interaction with cellular factors. Association of the protein AUF1 with an ARE-containing transcript targets the mRNA for decay, involving the assembly or recruitment of a multi-subunit trans-acting complex. In this chapter, recent evidence is described which indicates that recognition of ARE sequences by AUF1 induces dynamic protein oligomerization, which may serve as a scaffold for association of other cytoplasmic factors leading to catabolism of the RNA substrate. This mechanism of targeted trans-acting complex assembly may be regulated at several points, either involving differential expression of individual subunits or through the activity of selected signal transduction pathways. Finally, specific examples are described where alterations in the distribution of AUF1 isoforms lead to differential gene expression during development, and where accelerated mRNA turnover associated with enhanced AUF1 protein levels may contribute to the pathogenesis of congestive heart failure.
KeywordsmRNA Decay Heterogeneous Nuclear Ribonucleoprotein mRNA Turnover mRNA Metabolism mRNA Decay Rate
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