The study investigates the mechanism by which AU-rich elements (AREs) in mammalian mRNAs promote rapid degradation. The authors purified and characterized the human exosome, a 3'-to-5' exonuclease, and found that it is required for the rapid degradation of ARE-containing mRNAs but not for poly(A) shortening. The exosome does not recognize ARE-containing RNAs on its own; instead, it requires certain ARE-binding proteins (AUBPs) to recognize and recruit it to unstable RNAs. The AUBPs KSRP and TTP were shown to interact with the exosome and promote its recruitment to ARE-RNAs, thereby facilitating their degradation. The results suggest that the exosome and AUBPs work together to regulate mRNA turnover, with the exosome responsible for the 3'-to-5' decay pathway and AUBPs altering the interactions between RNA binding proteins and the mRNA, providing access to the exosome for degradation.The study investigates the mechanism by which AU-rich elements (AREs) in mammalian mRNAs promote rapid degradation. The authors purified and characterized the human exosome, a 3'-to-5' exonuclease, and found that it is required for the rapid degradation of ARE-containing mRNAs but not for poly(A) shortening. The exosome does not recognize ARE-containing RNAs on its own; instead, it requires certain ARE-binding proteins (AUBPs) to recognize and recruit it to unstable RNAs. The AUBPs KSRP and TTP were shown to interact with the exosome and promote its recruitment to ARE-RNAs, thereby facilitating their degradation. The results suggest that the exosome and AUBPs work together to regulate mRNA turnover, with the exosome responsible for the 3'-to-5' decay pathway and AUBPs altering the interactions between RNA binding proteins and the mRNA, providing access to the exosome for degradation.