A specific mRNA binding factor regulates the iron-dependent stability of cytoplasmic transferrin receptor mRNA.
Iron regulates human transferrin receptor (hTR) expression by modulating the stability of cytoplasmic hTR mRNA. This regulation requires a distinct secondary structure in the mRNA 3' untranslated region. We identified a specific cytoplasmic factor that binds simultaneously to four homologous palindromes within the regulatory domain. Iron chelator induced the RNA binding activity 25-fold in parallel with mRNA. Upon the addition of iron salts, a rapid decay of factor activity closely preceded hTR mRNA degradation, indicating a causal relation. Induction and decay occurred posttranscriptionally. Binding of the factor to hTR mRNA palindromes was competed by 5' regulatory sequences of ferritin mRNA, which are responsible for iron-dependent translational control. These results suggest that cellular iron maintains its homeostasis by coordinate regulation of hTR and ferritin expression via a common factor.
Müllner
E W
EW
Swiss Institute for Experimental Cancer Research Genetics Unit, Epalinges, Switzerland.
Neupert
B
B
Kühn
L C
LC
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D003593:Cytoplasm / Q000032:analysis / Q000648:ultrastructure; D005260:Female; D005293:Ferritins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007501:Iron / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D029543:Nucleocytoplasmic Transport Proteins; D010920:Placenta / Q000032:analysis / Q000166:cytology / Q000648:ultrastructure; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D016601:RNA-Binding Proteins; D011990:Receptors, Transferrin / Q000235:genetics*; D014158:Transcription, Genetic
D002352:Carrier Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron