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, whose stability is regulated through its AU-rich 3'-UTR. We demonstrate that the mammalian TNFalpha 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 TNFalpha 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.
Vasudevan
S
S
Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 08854, Piscataway, NJ, USA.
Peltz
S W
SW
D020413:3' Untranslated Regions / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015966:Gene Expression Regulation, Fungal; D017930:Genes, Reporter; D066298:In Vitro Techniques; D008322:Mammals; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000235:genetics; D039102:Poly(A)-Binding Proteins; D011108:Polymers / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology; D012331:RNA, Fungal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases; D000097574:Eukaryotic Translation Initiation Factor 5A
D020413:3' Untranslated Regions; D000241:Adenosine; D020928:Mitogen-Activated Protein Kinases; D010448:Peptide Initiation Factors; D039102:Poly(A)-Binding Proteins; D011108:Polymers; D016760:Proto-Oncogene Proteins c-fos; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000097574:Eukaryotic Translation Initiation Factor 5A; C083327:PUB1 protein, S cerevisiae; C069424:polyadenosine; C088589:HOG1 protein, S cerevisiae