Selenium regulation of transcript abundance and translational efficiency of glutathione peroxidase-1 and-4 in rat liver

Glutathione peroxidase (GPX) I mRNA in rat liver falls dramatically during Se deficiency to levels that are approx. 10 % of Se-adequate levels. This r egulation is mediated by mRNA stability, and is hypothesized to involve non sense-mediated mRNA decay. mRNA levels for GPX4 and other selenoproteins ar e much less regulated by Se status. To evaluate the relative contribution o f mRNA abundance versus translational efficiency to overall regulation of G PX1 expression, we quantified GPX1, GPX4 and glyceraldehyde-3-phosphate deh ydrogenase (GAPDH) transcripts per cell in rat liver. Surprisingly, we foun d that GPX1 transcripts in Se deficiency are moderately abundant and simila r in abundance to GAPDH and other selenoprotein mRNAs; Se supplementation i ncreases GPX1 mRNA so that it is 30-fold higher than GAPDH mRNA. Translatio nal efficiency of GPX1 mRNA is half of that of GPX4. Translational efficien cy of GPX1 mRNA increases approx. 20-fold with Se supplementation and appea rs to switch GPX1 mRNA from nonsense-mediated degradation to translation. T his regulatory switch can explain why GPX1 expression is an excellent param eter for assessment of Se status.