title: PP4 dephosphorylates Maf1 to couple multiple stress conditions to RNA polymerase III repression.
abstract: Maf1 is the 'master' repressor of RNA polymerase III (Pol III) transcription in yeast, and is conserved in eukaryotes. Maf1 is a phospho-integrator, with unfavourable growth conditions leading to rapid Maf1 dephosphorylation, nuclear accumulation, binding to RNA Pol III at Pol III genes and transcriptional repression. Here, we establish the protein phosphatase 4 (PP4) complex as the main Maf1 phosphatase, and define the involved catalytic (Pph3), scaffold (Psy2) and regulatory subunits (Rrd1, Tip41), as well as uninvolved subunits (Psy4, Rrd2). Multiple approaches support a central role for PP4 in Maf1 dephosphorylation, Maf1 nuclear localization and the rapid repression of Pol III in the nucleus. PP4 action is likely direct, as a portion of PP4 co-precipitates with Maf1, and purified PP4 dephosphorylates Maf1 in vitro. Furthermore, Pph3 mediates (either largely or fully) rapid Maf1 dephosphorylation in response to diverse stresses, suggesting PP4 plays a key role in the integration of cell nutrition and stress conditions by Maf1 to enable Pol III regulation.
authors.affiliation: HHMI, Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Oler
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Cairns
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D012320:RNA Polymerase III / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C104954:MAF1 protein, S cerevisiae; D009687:Nuclear Proteins; C494616:Psy2 protein, S cerevisiae; C502933:RRD2 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C444301:TIP41 protein, S cerevisiae; D014157:Transcription Factors; D012320:RNA Polymerase III; C531122:Psy4 protein, S cerevisiae; C502440:PPH3 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; C080406:protein phosphatase 4; D019696:Peptidylprolyl Isomerase; C490203:RRD1 protein, S cerevisiae