title: Repression of class I transcription by cadmium is mediated by the protein phosphatase 2A.
abstract: Toxic metals are part of our environment, and undue exposure to them leads to a variety of pathologies. In response, most organisms adapt their metabolism and have evolved systems to limit this toxicity and to acquire tolerance. Ribosome biosynthesis being central for protein synthesis, we analyzed in yeast the effects of a moderate concentration of cadmium (Cd(2+)) on Pol I transcription that represents >60% of the transcriptional activity of the cells. We show that Cd(2+) rapidly and drastically shuts down the expression of the 35S rRNA. Repression does not result from a poisoning of any of the components of the class I transcriptional machinery by Cd(2+), but rather involves a protein phosphatase 2A (PP2A)-dependent cellular signaling pathway that targets the formation/dissociation of the Pol I-Rrn3 complex. We also show that Pol I transcription is repressed by other toxic metals, such as Ag(+) and Hg(2+), which likewise perturb the Pol I-Rrn3 complex, but through PP2A-independent mechanisms. Taken together, our results point to a central role for the Pol I-Rrn3 complex as molecular switch for regulating Pol I transcription in response to toxic metals.
authors: CEA, iBiTecS, F-91191 Gif-sur-Yvette cedex, France.
authors: Lei
authors: L
authors: Zhou
authors: Gwenaëlle
authors: G
authors: Le Roux
authors: Cécile
authors: C
authors: Ducrot
authors: Stéphane
authors: S
authors: Chédin
authors: Jean
authors: J
authors: Labarre
authors: Michel
authors: M
authors: Riva
authors: Christophe
authors: C
authors: Carles
mesh_terms: D002104:Cadmium / Q000494:pharmacology*; D008628:Mercury / Q000494:pharmacology; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D012834:Silver / Q000494:pharmacology; D061785:Transcription Initiation, Genetic / Q000187:drug effects*
chemical_list: D035463:Pol1 Transcription Initiation Complex Proteins; C101161:RRN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D002104:Cadmium; D012834:Silver; D012318:RNA Polymerase I; D054648:Protein Phosphatase 2; D008628:Mercury
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