A secretory defect causes specific and significant transcriptional repression of both ribosomal protein and rRNA genes (K. Mizuta and J. R. Warner, Mol. Cell. Biol. 14:2493-2502, 1994), suggesting the coupling of plasma membrane and ribosome syntheses. In order to elucidate the molecular mechanism of the signaling pathway, we isolated a cold-sensitive mutant with a mutation in a gene termed RRS1 (regulator of ribosome synthesis), which appeared to be defective in the signaling pathway. The rrs1-1 mutation greatly reduced transcriptional repression of both rRNA and ribosomal protein genes that is caused by a secretory defect. RRS1 is a novel, essential gene encoding a nuclear protein of 203 amino acid residues that is conserved in eukaryotes. A conditional rrs1-null mutant was constructed by placing RRS1 under the control of the GAL1 promoter. Rrs1p depletion caused defects in processing of pre-rRNA and assembly of ribosomal subunits.Balanced synthesis of cellular components is required for normal cell growth. A temperature-sensitive mutation in SLY1, whose gene product is involved in endoplasmic reticulum-toGolgi trafficking (26), causes the transcriptional repression of both ribosomal protein and rRNA genes in Saccharomyces cerevisiae (20). Further examination using various sec mutants showed that a defect anywhere in the secretory pathway, from a step prior to insertion of the nascent peptide into the endoplasmic reticulum to a step involved in the formation of the plasma membrane, prevents the continued synthesis of the components of the ribosome. Similar results were obtained following treatment of wild-type cells with the secretory inhibitors tunicamycin and brefeldin A (20). Furthermore, many temperature-sensitive mutants in which transcription of ribosomal protein genes is temperature sensitive appear to be defective in the secretory pathway (17). As the membrane is the end product of much of the secretory pathway, these results suggest an important coupling of plasma membrane and ribosome biosynthesis. We proposed the existence of a signal transduction pathway from the plasma membrane to the nucleus. According to this model, a signal generated by the defect in de novo synthesis of membrane should be transmitted to the nucleus and cause specific and significant transcriptional repression of ribosomal genes. It was recently suggested that stress in the plasma membrane is monitored by Pkc1, which initiates a signal transduction pathway that leads to the repression (24). In order to elucidate the molecular mechanism of the signal transduction pathway, we have screened for mutants defective in the response to a secretory defect.Here we describe the isolation and molecular characterization of RRS1, encoding an essential nuclear protein of 203 amino acids. In the rrs1-1 mutant, a secretory defect fails to cause transcriptional repression of either rRNA or ribosomal protein genes. The mutant gene, rrs1-1, had a single nucleotide difference within codon 114, resulting in a stop codon. The amino acid sequence of R...

Background: A defect in the secretory pathway causes the transcriptional repression of both rRNA and ribosomal protein genes in Saccharomyces cerevisiae, suggesting a coupling of ribosome synthesis and plasma membrane synthesis. Rrs1p, an essential nuclear protein, is required for the secretory response.