17. The 5′ UTR of ferritin mRNA forms a stem-loop structure called the iron regulatory element (IRE). The Iron Regulatory Binding Protein [IRBP] binds this IRE. The following statements were made with reference to IRBP- IRE interaction:
(A) IRBP-IRE interaction prevents elF4A from resolving the stem-loop structure, thus preventing initiation of translation of ferritin genes.
(B) IRBP-IRE interaction recruits elF4A to the 5′ UTR, thus promoting translation initiation.
(C) In presence of ferrous ions IRBP is unable to bind the IRE.
(D) elF4A binds directly at the 5′ UTR and disrupts the stem-loop structure, thus promoting translation initiation.
Which one of the options below represents the combination of all correct statements?
(1) B only        (2) A and D
(3) A and C    (4) B and C

 

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Introduction

Iron homeostasis is vital for cellular function, and its regulation occurs at multiple levels, including translation of ferritin mRNA. Ferritin, an iron storage protein, is tightly controlled by the interaction of iron regulatory proteins (IRPs) with iron-responsive elements (IREs) in the 5′ untranslated region (UTR) of its mRNA. This interaction modulates translation initiation by affecting RNA secondary structure and the activity of translation factors such as eIF4A.

IRP-IRE Interaction and Translational Control

Under low iron conditions, IRPs bind to the stem-loop IRE in the 5′ UTR of ferritin mRNA. This binding stabilizes the stem-loop, preventing the RNA helicase eIF4A from resolving the structure. As a result, the ribosome scanning process is blocked, and translation initiation is inhibited, reducing ferritin synthesis when iron is scarce.

Effect of Iron on IRP Binding

When cellular iron levels rise, ferrous ions bind to IRPs, inducing conformational changes that reduce their affinity for IREs. This dissociation frees the mRNA, allowing eIF4A to unwind the stem-loop structure and promoting translation initiation. Consequently, ferritin protein levels increase to store excess iron safely.

Role of eIF4A in Translation Initiation

eIF4A is an ATP-dependent RNA helicase that binds to the 5′ UTR of mRNAs and unwinds secondary structures like stem-loops. This unwinding is crucial for ribosome scanning and efficient translation initiation, especially for mRNAs with structured 5′ UTRs such as ferritin.

Conclusion

The regulation of ferritin translation involves a delicate balance between IRP binding and iron availability. IRP binding to IREs inhibits translation by stabilizing RNA secondary structures and blocking eIF4A activity. Iron binding to IRPs reverses this inhibition, allowing eIF4A to promote translation initiation. This mechanism ensures cellular iron homeostasis by controlling ferritin protein synthesis in response to iron levels.

Correct answer:
(3) A and C

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This article summarizes the molecular interplay between IRPs, IREs, and eIF4A in regulating ferritin translation, highlighting the importance of RNA structure and iron sensing in gene expression control.