Structure and dynamics of the iron responsive element RNA: implications for binding of the RNA by iron regulatory binding proteins

Abstract

The iron responsive element (IRE) is a approximately 30 nucleotide RNA hairpin that is located in the 5' untranslated region of all ferritin mRNAs and in the 3' untranslated region of all transferrin receptor mRNAs. The IREs are bound by two related IRE-binding proteins (IRPs) which help control intracellular levels of iron by regulating the expression of both ferritin and transferrin receptor genes. Multi-dimensional NMR and computational approaches were used to study the structure and dynamics of the IRE RNA in solution. The NMR data are consistent with formation of A-form helical stem regions, a one-base internal bulge and a Watson-Crick C.G base-pair between the first and fifth nucleotides in the loop. A superposition of refined structures indicates that the conserved C in the internal bulge, and three residues in the six-nucleotide hairpin loop are quite dynamic in this RNA. The structural roles of the stems, the loop and the bulge in the function of the IRE RNA and in possible interactions with the iron regulatory protein are discussed.