General repression of RNA polymerase III transcription is triggered by protein phosphatase type 2A-mediated dephosphorylation of Maf1.
We report genome-wide analyses that establish Maf1 as a general and direct repressor of yeast RNA polymerase (Pol) III transcription. Chromatin immunoprecipitation (ChIP) coupled to microarray hybridization experiments showed an increased association of Maf1 to Pol III-transcribed genes under repressing condition (rapamycin treatment) correlated with a dissociation of Brf1 and Pol III. Maf1 can exist in various phosphorylation states and interacts with Pol III in a dephosphorylated state. The largest subunit of Pol III, C160, was identified as a target of Maf1. Under repressing conditions, Maf1 is dephosphorylated and accumulates in the nucleus, and Pol III-Maf1 interaction increases. Mutations in protein phosphatase type 2A (PP2A) catalytic subunit-encoding genes prevented rapamycin-induced Maf1 dephosphorylation, its nuclear accumulation, and repression of Pol III transcription. The results indicate that Pol III transcription can be globally and rapidly downregulated via dephosphorylation and relocation of a general negative cofactor.
Oficjalska-Pham
Danuta
D
Laboratoire de Transcription des Gènes, Service de Biochimie et Génétique Moléculaire, CEA/Saclay, 91191 Gif-sur-Yvette Cedex, France.
Harismendy
Olivier
O
Smagowicz
Wieslaw J
WJ
Gonzalez de Peredo
Anne
A
Boguta
Magdalena
M
Sentenac
André
A
Lefebvre
Olivier
O
D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D004794:Enzyme Repression / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D019913:Nuclear Localization Signals / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D021122:Protein Subunits / Q000378:metabolism; D012320:RNA Polymerase III / Q000037:antagonists & inhibitors* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000378:metabolism / Q000494:pharmacology; D035361:Transcription Factor TFIIIB / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
C104954:MAF1 protein, S cerevisiae; D019913:Nuclear Localization Signals; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D035361:Transcription Factor TFIIIB; D014157:Transcription Factors; D012320:RNA Polymerase III; D010749:Phosphoprotein Phosphatases; D020123:Sirolimus