Regulation of RNA polymerase III transcription involves SCH9-dependent and SCH9-independent branches of the target of rapamycin (TOR) pathway.
Maf1 is a conserved repressor of transcription that functions at the downstream end of multiple nutrient and stress signaling pathways. How these different signaling pathways converge on Maf1 is not known. Previous work in yeast indicates that protein kinase A (PKA) regulates RNA polymerase (pol) III transcription, in part, by phosphorylating multiple sites in Maf1. Here we present additional evidence for this view and show that a parallel nutrient and stress-sensing pathway involving Sch9, an homologous kinase to metazoan S6 kinase, targets Maf1 at a subset of PKA sites. Using ATP analog-sensitive alleles of PKA and Sch9, we find that these two kinases account for the bulk of the phosphorylation on consensus PKA sites in Maf1. Deletion of Sch9 reduces RNA pol III transcription in a Maf1-dependent manner, yet the cells remain susceptible to further repression by rapamycin and other treatments. Because the rapamycin-sensitive kinase activity of the TORC1 complex is necessary for Sch9 function in vivo and in vitro, our results show that transcriptional regulation of RNA pol III and the coordinate control of ribosomal protein genes can be achieved by Sch9-dependent and -independent branches of the target of rapamycin (TOR) signaling pathway.
Lee
Jaehoon
J
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Moir
Robyn D
RD
Willis
Ian M
IM
D015152:Blotting, Northern; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012320:RNA Polymerase III / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
C104954:MAF1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C530964:SCH9 protein, S cerevisiae; C500749:target of rapamycin protein, S cerevisiae; D017868:Cyclic AMP-Dependent Protein Kinases; D012320:RNA Polymerase III; D020123:Sirolimus