Phosphorylation of p40AUF1 regulates binding to A+U-rich mRNA-destabilizing elements and protein-induced changes in ribonucleoprotein structure

Messenger RNA turnover directed by A+U-rich elements (AREs) involves selected ARE-binding proteins. Whereas several signaling systems may modulate ARE-directed mRNA decay and/or post-translationally modify specific trans-acting factors, it is unclear how these mechanisms are linked. In THP-1 monocytic leukemia cells, phorbol ester-induced stabilization of some mRNAs containing AREs was accompanied by dephosphorylation of Ser(83) and Ser(87) of polysome-associated p40(AUF1). Here, we report that phosphorylation of p40(AUF1) influences its ARE-binding affinity as well as the RNA conformational dynamics and global structure of the p40(AUF1)-ARE ribonucleoprotein complex. Most notably, association of unphosphorylated p40(AUF1) induces a condensed RNA conformation upon ARE substrates. By contrast, phosphorylation of p40(AUF1) at Ser(83) and Ser(87) inhibits this RNA structural transition. These data indicate that selective AUF1 phosphorylation may regulate ARE-directed mRNA turnover by remodeling local RNA structures, thus potentially altering the presentation of RNA and/or protein determinants involved in subsequent trans-factor recruitment.