AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Mammalian mRNAs with AU-rich elements (AREs) in their 3' untranslated regions are inherently unstable. While the mechanism by which AREs regulate rapid mRNA decay is unclear, the yeast exosome mediates 3'-to-5' degradation. The human exosome, purified and characterized, shares structural similarity with the yeast exosome. It is required for the degradation of ARE-containing RNAs but not for poly(A) shortening. ARE recognition requires specific ARE-binding proteins (AUBPs) that interact with the exosome, recruiting it to unstable RNAs and promoting their degradation. AUBPs such as KSRP and TTP bind to AREs and recruit the exosome to facilitate 3'-to-5' degradation. The exosome is not required for deadenylation but is necessary for the degradation of deadenylated ARE-RNAs. AUBPs are essential for exosome-mediated degradation of ARE-RNAs, as their removal prevents this process. The exosome is associated with a putative RNA helicase, and its interaction with AUBPs is crucial for targeting it to ARE-RNAs. These findings highlight the role of the exosome in ARE-mediated mRNA decay and the importance of AUBPs in this process. The study provides insights into the mechanisms of mRNA turnover and the regulation of ARE-containing mRNAs.AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Mammalian mRNAs with AU-rich elements (AREs) in their 3' untranslated regions are inherently unstable. While the mechanism by which AREs regulate rapid mRNA decay is unclear, the yeast exosome mediates 3'-to-5' degradation. The human exosome, purified and characterized, shares structural similarity with the yeast exosome. It is required for the degradation of ARE-containing RNAs but not for poly(A) shortening. ARE recognition requires specific ARE-binding proteins (AUBPs) that interact with the exosome, recruiting it to unstable RNAs and promoting their degradation. AUBPs such as KSRP and TTP bind to AREs and recruit the exosome to facilitate 3'-to-5' degradation. The exosome is not required for deadenylation but is necessary for the degradation of deadenylated ARE-RNAs. AUBPs are essential for exosome-mediated degradation of ARE-RNAs, as their removal prevents this process. The exosome is associated with a putative RNA helicase, and its interaction with AUBPs is crucial for targeting it to ARE-RNAs. These findings highlight the role of the exosome in ARE-mediated mRNA decay and the importance of AUBPs in this process. The study provides insights into the mechanisms of mRNA turnover and the regulation of ARE-containing mRNAs.