Regulated ARE-mediated mRNA decay in Saccharomyces cerevisiae

Area of Science:

• Molecular Biology
• Gene Regulation
• Yeast Genetics

Background:

• RNA transcript stability is crucial for gene expression, particularly for oncogenes and growth factors.
• AU-rich elements (AREs) in the 3'-untranslated regions (3'-UTRs) are key regulators of transcript turnover.
• Understanding ARE-mediated decay (AMD) mechanisms is vital for comprehending cellular signaling.

Purpose of the Study:

• To investigate the role of AU-rich elements (AREs) in regulating transcript stability in yeast.
• To determine if conserved mechanisms exist for ARE-mediated decay between yeast and mammals.
• To explore the influence of nutrient availability and specific signaling pathways on ARE function.

Main Methods:

• Utilized a yeast reporter system to study the function of mammalian and yeast AREs.
• Manipulated glucose availability and inhibited the Hog1p/p38 MAP kinase pathway.
• Assessed transcript deadenylation and decapping rates.
• Investigated the role of the yeast ELAV homolog, Pub1p, in ARE-mediated decay.

Main Results:

• Mammalian TNFalpha and c-fos AREs regulated reporter transcript turnover in yeast.
• AREs stabilized transcripts in glucose-rich media but destabilized them in glucose-depleted media or upon p38 pathway inhibition.
• Both yeast and mammalian AREs promoted deadenylation-dependent decapping.
• Yeast Pub1p influenced TNFalpha ARE-mediated transcript stability.

Conclusions:

• Yeast possess a conserved, regulated mechanism for AU-rich element-mediated decay.
• Nutrient status and MAPK signaling pathways impact ARE-mediated transcript turnover.
• The findings suggest a conserved RNA decay pathway from yeast to humans.