A novel mRNA-decapping activity in HeLa cytoplasmic extracts is regulated by AU-rich elements

While decapping plays a major role in mRNA turnover in yeast, biochemical e vidence for a similar activity in mammalian cells has been elusive. We have now identified a decapping activity in HeLa cytoplasmic extracts that rele ases (7me)GDP from capped transcripts. Decapping is activated in extracts b y the addition of (7me)GpppG, which specifically sequesters cap-binding pro teins such as eIF4E and the deadenylase DAN/PARN. Similar to lit vivo obser vations, the presence of a poly(A) tail represses decapping of RNAs in vitr o in a poly(A)-binding protein-dependent fashion. AU-rich elements (AREs), which act as regulators of mRNA stability in vivo, are potent stimulators o f decapping in vitro. The stimulation of decapping by AREs requires sequenc e-specific ARE-binding proteins. These data suggest that cap recognition an d decapping play key roles in mediating mRNA turnover in mammalian cells.