NUTRIENT AVAILABILITY AND THE RAS CYCLIC AMP PATHWAY BOTH INDUCE EXPRESSION OF RIBOSOMAL-PROTEIN GENES IN SACCHAROMYCES-CEREVISIAE BUT BY DIFFERENT MECHANISMS/

By differential hybridization, we identified a number of genes in Sacc haromyces cerevisiae that are activated by addition of cyclic AMP (cAM P) to cAMP-depleted cells. A majority, but not all, of these genes enc ode ribosomal proteins. While expression of these genes is also induce d by addition of the appropriate nutrient to cells starved for a nitro gen source or for a sulfur source, the pathway for nutrient activation of ribosomal protein gene transcription is distinct from that of cAMP activation: (i) cAMP-mediated transcriptional activation was blocked by prior addition of an inhibitor of protein synthesis whereas nutrien t-mediated activation was not, and (ii) cAMP-mediated induction of exp ression occurred through transcriptional activation whereas nutrient-m ediated induction was predominantly a posttranscriptional response. Tr anscriptional activation of the ribosomal protein gene RPL16A by cAMP is mediated through a upstream activation sequence element consisting of a pair of RAP1 binding sites and sequences between them, suggesting that RAP1 participates in the cAMP activation process. Since RAP1 pro tein decays during starvation for cAMP, regulation of ribosomal protei n genes under these conditions may directly relate to RAP1 protein ava ilability. These results define additional critical targets of the cAM P dependent protein kinase, suggest a mechanism to couple ribosome pro duction to the metabolic activity of the cell, and emphasize that nutr ient regulation is independent of the RAS/cAMP pathway.