Repression of class I transcription by cadmium is mediated by the protein phosphatase 2A.

Lei Zhou, Gwenaëlle Le Roux, Cécile Ducrot, Stéphane Chédin, Jean Labarre, Michel Riva, Christophe Carles

Nucleic acids research 2013 Jul

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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.

Citation

Lei Zhou, Gwenaëlle Le Roux, Cécile Ducrot, Stéphane Chédin, Jean Labarre, Michel Riva, Christophe Carles. Repression of class I transcription by cadmium is mediated by the protein phosphatase 2A. Nucleic acids research. 2013 Jul;41(12):6087-97