AU-Rich Elements Regulate Drosophila Gene Expression

Abstract

In mammals, AU-rich elements (AREs) are critical regulators of mRNA turnover. They recruit ARE-binding proteins that inhibit or stimulate rapid mRNA degradation in response to stress or developmental cues. Using a bioinformatics approach, we have identified AREs in Drosophila melanogaster 3′ untranslated regions and validated their cross-species conservation in distant Drosophila genomes. We have generated a Drosophila ARE database (D-ARED) and established that about 16% of D. melanogaster genes contain the mammalian ARE signature, an AUUUA pentamer in an A/U-rich context. Using candidate ARE genes, we show that Drosophila AREs stimulate reporter mRNA decay in cultured cells and in the physiological context of the immune response in D. melanogaster . In addition, we found that the conserved ARE-binding protein Tis11 regulates temporal gene expression through ARE-mediated decay (AMD) in D. melanogaster . Our work reveals that AREs are conserved and functional cis regulators of mRNA decay in Drosophila and highlights this organism as a novel model system to unravel in vivo the contribution of AMD to various processes.