title: Regulation of ribonucleotide reductase in response to iron deficiency.
abstract: Ribonucleotide reductase (RNR) is an essential enzyme required for DNA synthesis and repair. Although iron is necessary for class Ia RNR activity, little is known about the mechanisms that control RNR in response to iron deficiency. In this work, we demonstrate that yeast cells control RNR function during iron deficiency by redistributing the Rnr2-Rnr4 small subunit from the nucleus to the cytoplasm. Our data support a Mec1/Rad53-independent mechanism in which the iron-regulated Cth1/Cth2 mRNA-binding proteins specifically interact with the WTM1 mRNA in response to iron scarcity and promote its degradation. The resulting decrease in the nuclear-anchoring Wtm1 protein levels leads to the redistribution of the Rnr2-Rnr4 heterodimer to the cytoplasm, where it assembles as an active RNR complex and increases deoxyribonucleoside triphosphate levels. When iron is scarce, yeast selectively optimizes RNR function at the expense of other non-essential iron-dependent processes that are repressed, to allow DNA synthesis and repair.
authors.affiliation: Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas, Burjassot, Valencia 46100, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Sanvisens
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Bañó
authors.forename: Mingxia
authors.initials: M
authors.lastname: Huang
authors.forename: Sergi
authors.initials: S
authors.lastname: Puig
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D064447:Checkpoint Kinase 2; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000090463:Iron Deficiencies; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport; D020871:RNA Stability; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D012262:Ribonucleoside Diphosphate Reductase / Q000737:chemistry / Q000378:metabolism*; D012264:Ribonucleotide Reductases / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D051816:Tristetraprolin / Q000378:metabolism
chemical_list: C102098:CTH1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D021122:Protein Subunits; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C091790:TIS11 protein, S cerevisiae; D014157:Transcription Factors; D051816:Tristetraprolin; C107277:Wtm1 protein, S cerevisiae; C570014:RNR2 protein, S cerevisiae; D012264:Ribonucleotide Reductases; D012262:Ribonucleoside Diphosphate Reductase; C523202:Rnr4 protein, S cerevisiae; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae