Characteristics of the Iron-responsive Element (IRE) Stems in the Untranslated Regions of Animal mRNAs

Bin Wang1, *, Michael S. Thompson1, Kevin M. Adkins1
1 Department of Chemistry, Marshall University, Huntington, WV 25755, United States

© 2021 Wang et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Chemistry, Marshall University, One John Marshall Drive, BBSC 241L, Huntington, WV 25755, United States; Tel: 001-304-696-3456; E-mail:



Iron-responsive Elements (IREs) are hairpin structures located in the 5’ or 3’ untranslated region of some animal mRNAs. IREs have a highly conserved terminal loop and a UGC/C or C bulge five bases upstream of the terminal loop, which divides the hairpin stem into an upper stem and a lower stem.


The objective of this study was to investigate the base-pair composition of the upper and lower stems of IREs to determine whether they are highly conserved among mRNAs from different genes.


The mRNA sequences of six 5’IREs and five 3’IREs from several animal species were retrieved from the National Center for Biotechnology Information. The folding free energy of each IRE mRNA sequence was predicted using the RNAfold WebServer.


We found that the upper and lower stems of IREs are not highly conserved among the mRNAs of different genes. There are no statistically significant differences in the IRE structures or folding free energies between mammalian and non-mammalian species relative to either the ferritin heavy chain 5’IRE or ferroportin 5’IRE. There are no overall significant differences in the folding free energies between UGC/C-containing 5’IREs and C-bulge-containing 5’IREs, or between 5’IREs and 3’IREs.


Further studies are needed to investigate whether the variations in IRE stem composition are responsible for fine-tuning the IRE/Iron-Regulatory Protein interactions among different mRNAs to maintain the balance of cellular iron metabolism, and to identify whether evolutionary processes drive the base-pair composition of the upper and lower stems of IREs toward any particular configuration.

Keywords: Iron-regulatory protein (IRP), Iron-responsive element (IRE), Untranslated region (UTR) of mRNA, IRE upper stem, IRE lower stem, Animal mRNA.