CONTROL OF MESSENGER-RNA TURNOVER AS A MECHANISM OF GLUCOSE REPRESSION IN SACCHAROMYCES-CEREVISIAE

The phenomenon of glucose repression in yeast is concerned. with the r epression of a large number of genes when glucose is an abundant carbo n source and almost all of the energy requirements of the cell can be satisfied from glycolysis. Prominent among the repressed genes are tho se encoding mitochondrial proteins required for respiration and oxidat ive phosphorylation. Past studies have characterized a pathway by whic h a signal generated from extracellular glucose is transmitted to the nucleus. The ultimate outcome is the repression of transcription of nu merous genes, but also the induction of a limited number of others. Th e emphasis has been almost exclusively on transcriptional control mech anisms. A discovery made originally with the transcript of the SDH2 ge ne prompted an investigation of post-transcriptional mechanisms, and m ore specifically a study of the turnover rate of this mRNA in the abse nce and presence of glucose. SDH2 mRNA has a very short half-life in m edium with glucose (YPD) and a significantly longer half-life in mediu m with glycerol (YPG). Experimental evidence and recent progress in un derstanding of (1) mRNA turnover in yeast and (2) initiation of transl ation on the 5' untranslated region of mRNAs, lead to a working hypoth esis with the following major features: the carbon source, via a signa ling pathway involving kinase/phosphatase activities, controls the rat e of initiation, and thus influences a competition between eukaryotic initiation factors (prominently eIF4E, eIF4G, eIF3) binding to the cap ped mRNA and a decapping activity (DCP1) which is one of the rate limi ting activities in the turnover of such mRNAs. (C) 1998 Elsevier Scien ce Ltd. All rights reserved.