Upper panel - Upf proteins regulate the stability of the mRNA encoding the magnesium transporter, Alr1. The uORFs in the 5’ leader of the ALR1 mRNA confer NMD sensitivity and regulate expression of the Alr1 transporter on the cell surface. This leads to normal magnesium levels in the cell, which in turn regulates the fidelity of the termination event at a premature termination codon.
Lower panel - In the absence of Upf proteins, ALR1 mRNA is stabilized due to loss of NMD. Stabilization of the mRNA leads to increased expression of Alr1 protein and increased uptake of magnesium. Elevated intracellular magnesium levels affect the fidelity of translation resulting in incorporation of a near cognate tRNA at PTCs, leading to nonsense suppression.