Tau mRNA iron-responsive element (Tau mRNA IRE)

The Tau mRNA iron-responsive element (IRE) is a conserved RNA stem-loop structure located within the 5' untranslated region (5' UTR) of the MAPT (Microtubule-associated protein tau) gene transcript (Cho et al., 2010, Journal of Biological Chemistry). It functions as a post-transcriptional regulator of Tau protein synthesis by interacting with iron regulatory proteins (IRPs), which modulate translation based on intracellular iron availability. Under conditions of low iron, IRPs bind to the IRE, sterically hindering the assembly of the ribosomal initiation complex and suppressing Tau synthesis. Conversely, elevated iron levels lead to IRP dissociation, allowing for increased Tau production. Dysregulation of this iron-sensing mechanism is a hallmark of Alzheimer's disease and other tauopathies, contributing to the pathological accumulation of Tau protein (Lei et al., 2012, Nature Medicine). Therapeutic agents such as Buntanetap (Posiphen) target this element to inhibit the translation of Tau and other neurotoxic proteins, offering a novel approach to treating neurodegeneration (Moussa et al., 2020, Journal of Neurochemistry).

Other names

MAPT 5' UTR iron-responsive elementTau 5'-UTR IRETau IRE

Inhibition of Tau protein translation by modulating the interaction between the iron-responsive element in the 5' UTR of MAPT mRNA and iron regulatory proteins.