Functional Link between the Mammalian Exosome and mRNA Decapping

Mechanistic understanding of mammalian mRNA turnover remains incomplete. We demonstrate that the 3′ to 5′ exoribonuclease decay pathway is a major contributor to mRNA decay both in cells and in cell extract. An exoribonuclease-dependent scavenger decapping activity was identified that follows decay of the mRNA and hydrolyzes the residual cap. The decapping activity is associated with a subset of the exosome proteins in vivo, implying a higher-order degradation complex consisting of exoribonucleases and a decapping activity, which together coordinate the decay of an mRNA. These findings indicate that following deadenylation of mammal mRNA, degradation proceeds by a coupled 3′ to 5′ exoribonucleolytic activity and subsequent hydrolysis of the cap structure by a scavenger decapping activity.