General Repression of RNA Polymerase III Transcription Is Triggered by Protein Phosphatase Type 2A-Mediated Dephosphorylation of Maf1

• Published in: Molecular cell Vol. 22; no. 5; pp. 623 - 632
• Main Authors: Oficjalska-Pham, Danuta, Harismendy, Olivier, Smagowicz, Wieslaw J., Gonzalez de Peredo, Anne, Boguta, Magdalena, Sentenac, André, Lefebvre, Olivier
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.06.2006; Cell Press
• Subjects: Cell Nucleus - drug effects; Cell Nucleus - metabolism; DNA; Down-Regulation; Enzyme Repression - genetics; Gene Expression Regulation, Fungal; Life Sciences; Nuclear Localization Signals - metabolism; Phosphoprotein Phosphatases - metabolism; Phosphorylation; Protein Subunits - metabolism; RNA Polymerase III - antagonists & inhibitors; RNA Polymerase III - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Signal Transduction; Sirolimus - metabolism; Sirolimus - pharmacology; Transcription Factor TFIIIB - metabolism; Transcription Factors - metabolism; Transcription, Genetic; DNA
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2006.04.008

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.