Jump to main content
Jump to site search

Issue 1, 2015
Previous Article Next Article

IRE mRNA riboregulators use metabolic iron (Fe2+) to control mRNA activity and iron chemistry in animals

Author affiliations

Abstract

A family of noncoding RNAs bind Fe2+ to increase protein synthesis. The structures occur in messenger RNAs encoding animal proteins for iron metabolism. Each mRNA regulatory sequence, ∼30 ribonucleotides long, is called an IRE (Iron Responsive Element), and folds into a bent, A-RNA helix with a terminal loop. Riboregulatory RNAs, like t-RNAs, r-RNAs micro-RNAs, etc. contrast with DNA, since single-stranded RNA can fold into a variety of complex, three-dimensional structures. IRE-RNAs bind two types of proteins: (1) IRPs which are protein repressors, sequence-related to mitochondrial aconitases. (2) eIF-4F, which bind ribosomes and enhances general protein biosynthesis. The competition between IRP and eIF-4F binding to IRE-RNA is controlled by Fe2+-induced changes in the IRE-RNA conformation. Mn2+, which also binds to IRE-RNA in solution, is a convenient experimental proxy for air-sensitive Fe2+ studies of in vitro protein biosynthesis and protein binding. However, only Fe2+ has physiological effects on protein biosynthesis directed by IRE-mRNAs. The structures of the IRE-RNA riboregulators is known indirectly from effects of base substitutions on function, from solution NMR of the free RNA, and of X-ray crystallography of the IRE-RNA–IRP repressor complex. However, the inability to date, to crystallize the free IRE-RNA, and the dissociation of the IRE-RNA–IRP complex when metal binds, have hampered direct identification and characterization of the RNA–metal binding sites. The high conservation of the primary sequence in IRE-mRNA control elements has facilitated their identification and analysis of metal-assisted riboregulator function. Expansion of RNA search analyses beyond primary will likely reveal other, metal-dependent families of mRNA riboregulators.

Graphical abstract: IRE mRNA riboregulators use metabolic iron (Fe2+) to control mRNA activity and iron chemistry in animals

Back to tab navigation

Publication details

The article was received on 12 May 2014, accepted on 02 Sep 2014 and first published on 11 Sep 2014


Article type: Minireview
DOI: 10.1039/C4MT00136B
Author version
available:
Download author version (PDF)
Metallomics, 2015,7, 15-24

  •   Request permissions

    IRE mRNA riboregulators use metabolic iron (Fe2+) to control mRNA activity and iron chemistry in animals

    E. C. Theil, Metallomics, 2015, 7, 15
    DOI: 10.1039/C4MT00136B

Search articles by author

Spotlight

Advertisements