Iron-responsive element-binding proteins (IRE-BPs)

Definition

Iron-responsive element-binding proteins (IRE-BPs) are regulatory proteins that bind to specific sequences known as iron-responsive elements (IREs) in mRNA, playing a crucial role in post-transcriptional regulation of gene expression related to iron metabolism. These proteins help maintain cellular iron homeostasis by controlling the translation of mRNAs involved in iron uptake, storage, and utilization, ensuring that the cell has the right amount of iron for its needs.

5 Must Know Facts For Your Next Test

1. IRE-BPs exist primarily in two forms: IRE-BP1 and IRE-BP2, with IRE-BP1 being the most studied and widely known for its role in regulating mRNA stability and translation.
2. The binding of IRE-BPs to IREs prevents the translation of ferritin mRNA when iron levels are low, while promoting the translation of transferrin receptor mRNA to increase iron uptake.
3. When cellular iron levels are sufficient, IRE-BPs undergo a conformational change that leads to their release from IREs, allowing ferritin translation to proceed and reducing transferrin receptor levels.
4. The regulation by IRE-BPs is crucial for preventing both iron deficiency and toxicity, as too much iron can generate harmful reactive oxygen species.
5. Changes in IRE-BP activity can be linked to various diseases, including anemia and neurodegenerative disorders, highlighting the importance of proper iron regulation.

Review Questions

• How do IRE-BPs regulate the translation of ferritin and transferrin receptor mRNAs based on cellular iron levels?
  • IRE-BPs regulate the translation of ferritin and transferrin receptor mRNAs by binding to their corresponding IREs. When cellular iron levels are low, IRE-BPs bind to the IREs of ferritin mRNA, inhibiting its translation to prevent excessive iron storage. At the same time, they promote the translation of transferrin receptor mRNA, enhancing iron uptake from the extracellular environment. This coordinated regulation ensures that cells maintain appropriate iron levels.
• Discuss how the activity of IRE-BPs can impact cellular responses to changing iron availability.
  • The activity of IRE-BPs directly influences how cells respond to fluctuations in iron availability. When iron is scarce, IRE-BPs stabilize transferrin receptor mRNA while repressing ferritin synthesis, thus facilitating increased iron absorption through transferrin receptors. Conversely, when there is enough iron, IRE-BPs release from their target mRNAs, allowing ferritin production to store excess iron safely. This dual regulatory mechanism allows cells to adapt dynamically to changing conditions of iron supply.
• Evaluate the potential consequences of dysregulation of IRE-BP function in relation to diseases associated with iron metabolism.
  • Dysregulation of IRE-BP function can have significant consequences for health, leading to disorders related to improper iron metabolism. For example, reduced IRE-BP activity may cause inadequate ferritin synthesis and result in iron overload, contributing to conditions like hemochromatosis. Alternatively, increased activity may lead to insufficient transferrin receptor levels and subsequent anemia due to reduced iron uptake. Understanding these mechanisms highlights the critical role that precise regulation of IRE-BPs plays in maintaining overall cellular health and preventing disease.

Related terms

Iron-responsive elements (IREs): Short sequences found in the untranslated regions (UTRs) of certain mRNAs that IRE-BPs bind to in order to regulate their stability and translation based on cellular iron levels.

Ferritin: A protein complex that stores iron and releases it in a controlled fashion; its translation is regulated by IRE-BPs in response to cellular iron levels.

Transferrin receptor: A membrane protein that mediates the uptake of iron-bound transferrin; its expression is increased when IRE-BPs are bound to IREs, promoting iron intake when needed.