The Hairpin Loop but Not the Bulged C of the Iron Responsive Element Is Essential for High Affinity Binding to Iron Regulatory Protein-1

Heather A. Meehan, Gregory J. Connell

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Vertebrates control intracellular iron concentration principally through the interaction of iron regulatory proteins with mRNAs that contain an iron responsive element, a small hairpin with a bulged C. The hairpin loop and bulged C have previously been assumed to be critical for binding and have been proposed to make direct contact with the iron regulatory proteins. However, we show here that a U or G can be substituted for the bulged C provided that specific nucleotides are also present within internal loops. The Kd, IC50 and chemical modifications of the iron responsive element variants are similar to the wild-type. Results are more consistent with a role in which the C-bulge functions to orient the hairpin for optimal protein binding rather than to directly contact the protein. Characterization of these novel iron responsive element variants may facilitate the identification of additional mRNAs whose expression is controlled by iron regulatory proteins, as well as provide insight into the nature of a critical RNA-protein interaction.

Original languageEnglish (US)
Pages (from-to)14791-14796
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number18
DOIs
StatePublished - May 4 2001

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