Structural requirements of iron-responsive elements for binding of the protein involved in both transferrin receptor and ferritin mRNA post-transcriptional regulation

Nucleic Acids Res. 1990 Apr 11;18(7):1819-24. doi: 10.1093/nar/18.7.1819.


The synthesis of both transferrin receptor (TfR) and ferritin is regulated post-transcriptionally by iron. This is mediated by iron responsive elements (IREs) in the 5'- and 3'-untranslated regions, respectively, of TfR and ferritin mRNAs. Although these IREs have different sequences, they both form a characteristic stem-loop. We used competition assays and partial peptide mapping of UV-crosslinked ferritin and TfR IRE-protein complexes to show that the cytosolic protein binding to the ferritin 5'-IRE, the iron-responsive element binding protein (IRE-BP), also binds to TfR 3'-IREs. To identify the structural requirements necessary for RNA-protein binding, ferritin IRE RNAs were synthesized which contained altered secondary structures and base substitutions. Affinities of these RNAs for IRE-BP were assayed in RNA-protein binding gels. Substitutions disrupting base-pairing of the stem prevented IRE-BP binding. Substitutions which restored base-pairing also restored IRE-BP binding. We conclude that the IRE-BP binds to both ferritin and TfR IREs and recognizes a particular IRE conformation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Carrier Proteins / metabolism*
  • Cytosol / metabolism
  • Ferritins / genetics*
  • Gene Expression Regulation / drug effects
  • Iron / pharmacology*
  • Liver / metabolism
  • Male
  • Molecular Sequence Data
  • Mutation
  • Nucleic Acid Conformation
  • RNA Processing, Post-Transcriptional* / drug effects
  • RNA, Messenger / genetics*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Transferrin / genetics*
  • Transcription, Genetic


  • Carrier Proteins
  • RNA, Messenger
  • Receptors, Transferrin
  • Ferritins
  • Iron