Nucleic Acids Research, 1990, Vol. 18, No. 7 1819-1824
© 1990
GENOME STRUCTURE AND MAPPING |
Structural requirements of iron-responsive elements for binding of the protein involved in both transferrin receptor and ferritin mRNA post-transcriptional regulation
Department of Medicine, Division of Hematology/Oncology, University of Utah School of Medicine Sah Lake Crty, UT 84132 1Department of Biochemistry, University of New Hampshire Durham, NH 03824, USA
Received November 21, 1989. Revised February 20, 1990. Accepted February 20, 1990.
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 competttion 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.
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