positive regulation of translational initiation by iron

Definition

Target type: biologicalprocess

Any process involving iron that activates or increases the rate of translational initiation. [GOC:go_curators]

Iron is an essential cofactor for numerous proteins involved in fundamental cellular processes, including DNA synthesis, respiration, and translation. The availability of iron can significantly influence the rate of protein synthesis, with iron deficiency leading to a decrease in protein synthesis and iron overload causing a disruption in cellular homeostasis. The positive regulation of translational initiation by iron involves a complex interplay of molecular players, including the iron-responsive element (IRE), iron regulatory proteins (IRP1 and IRP2), and the eukaryotic initiation factor 4E (eIF4E).

IREs are specific RNA sequences found in the 5' untranslated region (UTR) of mRNAs encoding proteins involved in iron metabolism. These IREs act as binding sites for IRPs, which are cytoplasmic proteins that sense cellular iron levels. When cellular iron levels are low, IRPs bind to IREs with high affinity. This binding event can either block the translation of mRNAs containing IREs in their 5' UTR or stabilize the mRNAs containing IREs in their 3' UTR.

In the case of mRNAs encoding proteins involved in iron uptake, such as the transferrin receptor (TfR), the binding of IRPs to the IREs in their 5' UTRs inhibits their translation. This prevents the synthesis of proteins that increase iron uptake when iron levels are already low. Conversely, in the case of mRNAs encoding proteins involved in iron storage, such as ferritin, the binding of IRPs to the IREs in their 5' UTRs stabilizes these mRNAs, preventing their degradation. This ensures that the mRNAs encoding iron storage proteins are available for translation when iron levels increase, allowing for the storage of excess iron.

When cellular iron levels are high, iron binds to IRPs, causing a conformational change that reduces their affinity for IREs. This allows the translation of mRNAs encoding iron uptake proteins, increasing iron uptake. It also destabilizes the mRNAs encoding iron storage proteins, reducing their translation. This ensures that iron levels remain within a narrow range that is optimal for cellular function.

eIF4E is a key regulator of translation initiation. It binds to the 5' cap structure of mRNAs, promoting their recruitment to ribosomes. Iron can positively regulate translation initiation by influencing the activity of eIF4E. In some cases, iron can promote the binding of eIF4E to mRNAs, thereby enhancing translation initiation. The exact mechanism by which iron influences eIF4E activity is still under investigation but may involve iron-dependent phosphorylation events or the interaction of iron with specific regulatory proteins that control eIF4E activity.

In summary, positive regulation of translational initiation by iron is a complex process that involves the interplay of multiple factors, including iron-responsive elements (IREs), iron regulatory proteins (IRPs), and the eukaryotic initiation factor 4E (eIF4E). This regulatory mechanism ensures that the synthesis of proteins involved in iron metabolism is tightly controlled in response to changes in cellular iron levels, allowing for the efficient utilization of iron for essential cellular processes.'
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Proteins (1)

Compounds (18)