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Selective Decrease in Regulatory Iron Response Protein 1 (IRP1) binding to mRNA Iron Response Element (IRE)
Author(s) -
KHAN MATEEN AHMAD,
WALDEN WILLIAM E,
THEIL ELIZABETH C,
GOSS DIXIE J
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.845.2
Subject(s) - ferritin , aconitase , messenger rna , rna binding protein , rna , untranslated region , translation (biology) , translational regulation , chemistry , in vivo , polysome , microbiology and biotechnology , binding protein , protein biosynthesis , biochemistry , biology , ribosome , gene , mitochondrion , genetics
In mRNA a family of 5' noncoding structures, iron response elements (IRE), control mRNA translation and protein biosynthesis rates by regulatory protein (IRP) binding when iron concentrations decrease. IRP protein represses translation by binding to the IRE and inhibiting formation of polysomes. We explored the extent to which the phylogentically conserved sequence differences among members of the IRE mRNA family related to differences in signal responses observed in vivo , since the regulatory proteins are the same for each mRNA. We selected two members of the IRE‐RNA family, ferritin and mitochondrial (mt‐) aconitase, to study effects on the 5' UTR IRE‐RNA sequence and IRP1 protein binding because of extensive structural information available, and because the iron responses in vivo range from 4‐fold for mt‐acontitase to more than 100‐fold for ferritin. We report here the binding affinity of IRP1 protein to ferritin and mt‐aconitase mRNA. The relative binding affinities varied dramatically depending on experimental conditions. Selective destabilization of ferritin and mt‐aconitase RNA/protein complexes as reported here explain in part the quantitative differences in signal response to iron in vivo and indicate possible new regulatory interactions.