Regulated ARE-mediated mRNA decay in Saccharomyces cerevisiae

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, w hose stability is regulated through its AU-rich 3'-UTR. We demonstrate that the mammalian TNF alpha and c-fos AREs regulate turnover of a reporter yea st transcript in a similar manner. AREs stabilize the transcript in glucose media and function as destabilizing elements in media lacking glucose or w hen the Hog1p/p38 MAP kinase pathway is inhibited. Significantly, both yeas t and mammalian AREs promote deadenylation-dependent decapping in the yeast system. Furthermore, the yeast ELAV homolog, Pub1p, regulates the stabilit y mediated by the TNF alpha ARE. These results demonstrate that yeast posse ss a regulatable mechanism for ARE-mediated decay and suggest conservation of this turnover process from yeast to humans.