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The following observations are being made in the context of the regulation of iron homeostasis in mammalian cells:(a) The levels of transferrin recept
Question

The following observations are being made in the context of the regulation of iron homeostasis in mammalian cells:

(a) The levels of transferrin receptor mRNA increase 30-fold in the absence of iron
(b) Certain mutations in the 3’UTR of transferrin receptor mRNA fail to support increase in mRNA levels under low iron concentrations
(c) The level of transferrin receptor mRNA continues to be high in low iron concentration even when the cells are treated with α-amanitin
(d) The transferrin receptor mRNA levels decrease rapidly when iron is added to the cells

Based on these observations, which one of the following statements represents the most likely scenario?

A.

Transferrin receptor is only transcriptionally regulated, and the 3’ end of the gene is the regulatory site

B.

Transferrin receptor is post-transcriptionally regulated, and the 3’UTR is the regulatory site

C.

Iron induces expression of transferrin receptor, and the transferrin receptor protein is degraded in the presence of iron

D.

Regulation of transferrin receptor is not sensitive to iron

Correct option is B

Explanation-

The transferrin receptor (TfR) helps cells uptake iron by binding transferrin-bound iron and internalizing it. Cells regulate TfR expression depending on iron availability, not at the transcriptional level, but at the mRNA stability level — a form of post-transcriptional regulation.
A. TfR mRNA increases 30-fold in absence of iron - This happens because iron regulatory proteins (IRPs) bind to iron response elements (IREs) in the 3′ UTR of the TfR mRNA. This prevents degradation of the mRNA → accumulation.
B. Mutations in the 3′UTR prevent this mRNA increase  - This confirms that 3′UTR is the regulatory region. Mutations here impair IRE-IRP interaction, preventing stabilization.
C. High TfR mRNA despite α-amanitin treatment (a transcription inhibitor) - mRNA remains high in low iron even when transcription is blocked, showing regulation is post-transcriptional (mRNA is stabilized, not newly transcribed).
D. TfR mRNA decreases rapidly when iron is added - Iron causes IRPs to release the 3′UTR → exposes it to endonucleolytic degradation, leading to mRNA decay.

Final answer -
Transferrin receptor expression is regulated post-transcriptionally via elements in the 3′UTR, which modulate mRNA stability in response to iron — making Option b the most accurate choice.

Option b - Transferrin receptor is post-transcriptionally regulated, and the 3’UTR is the regulatory site.

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