The 5'-untranslated region of human transferrin mRNA, which contains a putative iron-regulatory element, is bound by purified iron-regulatory protein in a sequence-specific manner.
Human transferrin mRNA contains a 5'-untranslated region that (1) has homology to an iron responsive element and (2) is implicated in translational iron regulation of human transferrin transgenes in transgenic mice. Ferritin mRNA contains a 5'-untranslated region iron-responsive element, but iron regulation of ferritin differs from that of human transferrin transgenes in both magnitude and direction. Structural differences between the ferritin iron-responsive element and the human transferrin putative iron-responsive element may influence their iron-regulatory protein interactions and direct the differing translational responses. This study examines human transferrin RNA nucleotide sequence requirements for binding of cytoplasmic proteins and purified iron-regulatory protein. Mutations of the putative transferrin iron-responsive element similarly affected binding of purified iron-regulatory protein and liver cytoplasmic proteins, providing evidence that the IRP is one of the liver cytoplasmic proteins that binds the human transferrin iron-regulatory element and suggesting that it may be involved in iron-regulation of transferrin.
Cox
L A
LA
Department of Molecular Medicine, University of Texas Health Science Center, San Antonio 78245-3207, USA.
Kennedy
M C
MC
Adrian
G S
GS
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D005293:Ferritins / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014168:Transferrin / Q000235:genetics*
D035925:Iron-Regulatory Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014168:Transferrin; D005293:Ferritins; D007501:Iron