The mRNA-binding protein which controls ferritin and transferrin receptor expression is conserved during evolution

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Biochemistry

Background:

• A protein known as iron regulatory factor (IRF) regulates iron levels post-transcriptionally in human and mouse cells.
• IRF binds to specific elements in ferritin and transferrin receptor mRNA, influencing their stability and translation.
• Low intracellular iron activates IRF, inhibiting ferritin translation and increasing transferrin receptor mRNA stability.

Purpose of the Study:

• To determine if the feedback regulatory mechanisms involving IRF are conserved across different species.
• To investigate the presence and properties of IRF-like proteins in a wide range of organisms.

Main Methods:

• Analysis of cytoplasmic extracts from 12 different species.
• Gel-retardation assays using radiolabeled RNA transcripts to detect specific mRNA-binding activity.
• Competition experiments, molecular weight determinations, and functional assays (response to iron levels, beta-mercaptoethanol).

Main Results:

• mRNA-binding proteins with specific iron-responsive element (IRE) binding activity were identified in chicken, frog, fish, and fly.
• These proteins showed similar characteristics to human and mouse IRF in gel-retardation assays.
• Competition assays and molecular weight determinations confirmed the similarity.
• The mRNA-binding activity was modulated by intracellular iron levels and beta-mercaptoethanol, similar to mammalian IRF.

Conclusions:

• The iron regulatory factor (IRF) and its regulatory functions are conserved across a wide range of species, from invertebrates to vertebrates.
• These findings suggest that the fundamental mechanisms of cellular iron homeostasis are evolutionarily ancient.
• The structural and functional properties of IRF are conserved, highlighting its critical role in iron metabolism throughout evolution.