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Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation
J L Casey1, M W Hentze, D M Koeller
1Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892.
Science (New York, N.Y.)
|May 13, 1988
Summary
Iron regulates gene expression by controlling protein synthesis. Researchers found a specific region in transferrin receptor (TfR) mRNA that dictates iron-dependent mRNA levels, revealing new insights into cellular iron homeostasis.
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- Cellular iron levels are tightly regulated by specific proteins.
- Ferritin and transferrin receptor (TfR) biosynthesis are key to iron homeostasis.
- Iron-responsive element (IRE) in ferritin mRNA controls translation based on iron availability.
Purpose of the Study:
- To investigate the mechanism of iron-dependent regulation of transferrin receptor (TfR) mRNA levels.
- To identify the specific sequences within TfR mRNA responsible for iron regulation.
- To explore the role of mRNA elements in mediating distinct regulatory phenomena.
Main Methods:
- Deletion studies of the human TfR complementary DNA (cDNA).
- Identification of critical regulatory fragments within the TfR mRNA.
- Insertion of TfR elements into an indicator gene transcript to assess function.
Main Results:
- The 3' untranslated region of TfR mRNA is essential and sufficient for iron-dependent control of mRNA levels.
- A 678-nucleotide fragment within the TfR mRNA was identified as critical for iron regulation.
- Five potential stem-loop structures resembling ferritin IREs were found in the critical TfR region.
- Two of these TfR elements conferred iron regulation of translation when placed in the 5' untranslated region of an indicator gene.
Conclusions:
- An mRNA element can mediate different regulatory outcomes (mRNA levels vs. translation) based on its location.
- The identified TfR mRNA elements play a crucial role in cellular iron regulation.
- This study implicates mRNA structure and location in complex gene expression control.