Cooperation of two mRNA-binding proteins drives metabolic adaptation to iron deficiency.
Iron (Fe) is an essential cofactor for a wide range of cellular processes. We have previously demonstrated in yeast that Cth2 is expressed during Fe deficiency and promotes degradation of a battery of mRNAs leading to reprogramming of Fe-dependent metabolism and Fe storage. We report here that the Cth2-homologous protein Cth1 is transiently expressed during Fe deprivation and participates in the response to Fe deficiency through the degradation of mRNAs primarily involved in mitochondrially localized activities including respiration and amino acid biosynthesis. In parallel, wild-type cells, but not cth1Deltacth2Delta cells, accumulate mRNAs encoding proteins that function in glucose import and storage and store high levels of glycogen. In addition, Fe deficiency leads to phosphorylation of Snf1, an AMP-activated protein kinase family member required for the cellular response to glucose starvation. These studies demonstrate a metabolic reprogramming as a consequence of Fe starvation that is dependent on the coordinated activities of two mRNA-binding proteins.
Puig
Sergi
S
Departament de Bioquímica i Biologia Molecular, Universitat de València, E-46100 Burjassot, València, Spain. sergi.puig@uv.es
Vergara
Sandra V
SV
Thiele
Dennis J
DJ
D000222:Adaptation, Physiological; D004268:DNA-Binding Proteins / Q000502:physiology*; D000090463:Iron Deficiencies; D008660:Metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D051816:Tristetraprolin / Q000502:physiology*
C102098:CTH1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C091790:TIS11 protein, S cerevisiae; D014157:Transcription Factors; D051816:Tristetraprolin; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases