Identification of the Iron-Responsive Element for the Translational Regulation of Human Ferritin mRNA

TLDR

Regulated translation of mRNA controls gene expression, and ferritin biosynthesis is regulated by iron. The study identifies the iron‑responsive element (IRE) in ferritin H‑chain mRNA and proposes its use in translationally regulated expression systems. The IRE was identified by deletional analysis of the 5′ nontranslated leader region. The 5′ leader of ferritin H‑chain mRNA contains a cis‑acting IRE that is necessary and sufficient for iron regulation, can be transferred by a synthetic oligodeoxynucleotide, and is highly conserved across vertebrates.

Abstract

Regulated translation of messenger RNA offers an important mechanism for the control of gene expression. The biosynthesis of the intracellular iron storage protein ferritin is translationally regulated by iron. A cis -acting element that is both necessary and sufficient for this translational regulation is present within the 5′ nontranslated leader region of the human ferritin H-chain messenger RNA. In this report the iron-responsive element (IRE) was identified by deletional analysis. Moreover, a synthetic oligodeoxynucleotide was shown to be able to transfer iron regulation to a construct that would otherwise not be able to respond to iron. The IRE has been highly conserved and predates the evolutionary segregation between amphibians, birds, and man. The IRE may prove to be useful for the design of translationally regulated expression systems.