title: RNA polymerase I stability couples cellular growth to metal availability.
abstract: Zinc is an essential cofactor of all major eukaryotic RNA polymerases. How the activity of these enzymes is coordinated or regulated according to cellular zinc levels is largely unknown. Here we show that the stability of RNA polymerase I (RNAPI) is tightly coupled to zinc availability in vivo. In zinc deficiency, RNAPI is specifically degraded by proteolysis in the vacuole in a pathway dependent on the export in Xpo1p and deubiquitination of the RNAPI large subunit Rpa190p by Ubp2p and Ubp4p. RNAPII is unaffected, which allows for the expression of genes required in zinc deficiency. RNAPI export to the vacuole is required for survival during zinc starvation, suggesting that degradation of zinc-binding subunits might provide a last resort zinc reservoir. These results reveal a hierarchy of cellular transcriptional activities during zinc starvation and show that degradation of the most active cellular transcriptional machinery couples cellular growth and proliferation to zinc availability.
authors.affiliation: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569, USA.
authors.forename: Yueh-Jung
authors.initials: YJ
authors.lastname: Lee
authors.forename: Chrissie Young
authors.initials: CY
authors.lastname: Lee
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Grzechnik
authors.forename: Fernando
authors.initials: F
authors.lastname: Gonzales-Zubiate
authors.forename: Ajay A
authors.initials: AA
authors.lastname: Vashisht
authors.forename: Albert
authors.initials: A
authors.lastname: Lee
authors.forename: James
authors.initials: J
authors.lastname: Wohlschlegel
authors.forename: Guillaume F
authors.initials: GF
authors.lastname: Chanfreau
mesh_terms: D015536:Down-Regulation; D010450:Endopeptidases / Q000378:metabolism / Q000502:physiology; D004795:Enzyme Stability; D012318:RNA Polymerase I / Q000378:metabolism / Q000502:physiology*; D012335:RNA, Ribosomal / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D054875:Ubiquitination; D014617:Vacuoles / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D012335:RNA, Ribosomal; D012318:RNA Polymerase I; D010450:Endopeptidases; C059237:ubiquitin-Nalpha-protein hydrolase; D015032:Zinc