Abstract The stability of several oncogene, cytokine, and growth factor transcripts is tightly regulated by signaling pathways through an ARE (AU-rich element) present in their 3′-UTRs. We have identified a yeast transcript, TIF51A, whose stability is regulated through its AU-rich 3′-UTR. We demonstrate that the mammalian TNFα and c -fos AREs regulate turnover of a reporter yeast transcript in a similar manner. AREs stabilize the transcript in glucose media and function as destabilizing elements in media lacking glucose or when the Hog1p/p38 MAP kinase pathway is inhibited. Significantly, both yeast and mammalian AREs promote deadenylation-dependent decapping in the yeast system. Furthermore, the yeast ELAV homolog, Pub1p, regulates the stability mediated by the TNFα ARE. These results demonstrate that yeast possess a regulatable mechanism for ARE-mediated decay and suggest conservation of this turnover process from yeast to humans.