The secondary structure of the regulatory region of the transferrin receptor mRNA deduced by enzymatic cleavage.

The secondary structure of the portion of the transferrin receptor mRNA responsible for the regulation of the transcript's half-life has been deduced by ribonuclease H cleavage directed by antisense oligodeoxyribonucleotides as well as with other ribonucleases sensitive to RNA secondary structure. The data indicate that both a synthetic 252-nucleotide RNA and the comparable portion of a 2.7-kb cellular mRNA contain three stem-loops referred to as iron-responsive elements (IREs). This secondary structure appears to be relatively static, with little interconversion with another possible structure having a similar calculated free energy but involving longer-range base pairing. Deletion of a selected cytosine residue from each of the IRE loops has been shown to yield an unregulated, unstable mRNA. This altered RNA has a secondary structure similar, if not identical, to that of the RNA that is competent in regulation.