Question

Iron is essential for the cell but potentially toxic. It is maintained at optimal levels in mammalian cells by the actions of three proteins. Transferrin receptors bind iron-loaded transferrin molecules and bring them into the cell. Any excess iron is then moved to ferritin complexes, which form cages that sequester up to 4500 iron atoms each.

The transferrin receptor and ferritin are regulated by iron-response proteins (IRPs) that bind to hairpin-forming iron-response elements (IREs) in their mRNAs. In both cases, IRPs bind to IREs only when iron levels are low, but the consequences of binding are exactly opposite. Binding of IRP to an IRE increases translation of the transferrin receptor, but it decreases translation of ferritin.
IREs in the transferrin receptor mRNA are located in the 3′ untranslated region of the mRNA (instead of at the 5′ end, as in ferritin mRNA). In the presence of iron, the transferrin receptor mRNA is rapidly degraded; in the absence of iron, it is stable.
Which one of the following hypotheses accounts for how iron levels might be linked to the stability of transferrin receptor mRNA?

Answer 1

The stability of transferrin receptor mRNA is hypothesized to be regulated by the binding of iron-response proteins to its iron-response elements. In low iron conditions, these proteins bind and stabilize the mRNA, but in high iron conditions, the binding decreases, leading to mRNA degradation.

Step-by-step explanation:

Iron levels are essential for cellular function and are maintained through a complex regulatory system involving proteins such as transferrin receptors and ferritin. Transferrin receptors bind iron-loaded transferrin to import iron into the cell, whereas excess iron is stored in ferritin complexes. The stability and translation of the mRNAs for these proteins are regulated by iron-response proteins (IRPs) that respond to cellular iron levels. IRPs bind to iron-response elements (IREs) in the mRNAs, with different consequences depending on their locations. Specifically, IRP binding to IREs in the 3′ untranslated region of transferrin receptor mRNA enhances its stability and translation in conditions of low iron, while IRP binding to IREs in the ferritin mRNA blocks translation initiation.

The hypothesis that could account for how iron levels are linked to the stability of transferrin receptor mRNA suggests that low iron levels lead to increased binding of IRPs to IREs in transferrin receptor mRNA, stabilizing the mRNA and enhancing receptor production. Conversely, high iron levels result in reduced IRP binding, leading to rapid mRNA degradation and a decrease in receptor production. The degradation of transferrin receptor mRNA in the presence of iron provides a feedback mechanism to tightly regulate iron uptake, ensuring that the element is available in sufficient quantities for cellular processes while preventing iron overload, which can be toxic.

Understanding this regulatory mechanism is crucial because disturbances in iron metabolism can lead to conditions such as anemia or iron overload disorders. Therefore, the link between iron levels and the stability of related mRNAs is a vital aspect of cellular iron homeostasis.