title: The mRNA-binding protein which controls ferritin and transferrin receptor expression is conserved during evolution.
abstract: A post-transcriptional regulatory protein, termed iron regulatory factor (IRF), that binds specifically to the iron-responsive elements of ferritin and transferrin receptor mRNA, has recently been identified in the cytoplasm of human and mouse cells. Activation of this factor by low intracellular iron levels leads to inhibition of ferritin translation and an increase of TR mRNA stability. To investigate whether these feedback regulatory mechanisms are conserved during evolution, we analysed cytoplasmic extracts from 12 different species for a specific IRE-binding activity. We found mRNA-binding proteins in chicken, frog, fish and fly, which are equivalent to human and mouse IRF in gel-retardation assays with radiolabeled RNA transcripts. Competition experiments, molecular weight determinations, and modulation of the mRNA-binding activity in response to intracellular iron levels or reduction by beta-mercaptoethanol indicate that IRF has similar structural and functional properties in these different species.
authors.affiliation: Swiss Institute for Experimental Cancer Research, Genetics Unit, Epalinges.
authors.forename: S
authors.initials: S
authors.lastname: Rothenberger
authors.forename: E W
authors.initials: EW
authors.lastname: Müllner
authors.forename: L C
authors.initials: LC
authors.lastname: Kühn
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D005075:Biological Evolution; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D003593:Cytoplasm / Q000378:metabolism; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation; D006801:Humans; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins; D035925:Iron-Regulatory Proteins; D051379:Mice; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface / Q000235:genetics*; D011990:Receptors, Transferrin / Q000235:genetics*; D014982:Xenopus laevis
chemical_list: D002352:Carrier Proteins; D033862:Iron-Binding Proteins; D035925:Iron-Regulatory Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; C027293:ferritin receptor; D007501:Iron