ROLE OF THE 3'-UNTRANSLATED REGION IN THE REGULATION OF CYTOSOLIC GLUTATHIONE-PEROXIDASE AND PHOSPHLIPID-HYDROPEROXIDE GLUTATHIONE-PEROXIDASE GENE-EXPRESSION BY SELENIUM SUPPLY

Selenium is an essential nutrient and synthesis of selenoproteins is a ffected by limited selenium supply. During selenium deficiency there i s a differential regulation of selenoprotein synthesis and gene expres sion; for example, there is a decrease in abundance of mRNA for cytoso lic glutathione peroxidase (cGSH-Px) and a preservation of mRNA for ph ospholipid-hydroperoxide glutathione peroxidase (PHGSH-Px). This diffe rence is not due to an alteration in the rate of transcription but mig ht reflect differences in translation. The aim of the present work was to assess the role of cGSH-Px and PHGSH-Px 3' untranslated regions (U TRs) in the regulation of selenoprotein mRNA stability and translation by using H4-II-E-C3 cells transfected with different constructs conta ining a type I iodothyronine deiodinase-coding region linked to differ ent selenoprotein mRNA 3' UTRs. Translational efficiency results showe d that the efficiency of the 3' UTRs in permitting selenocysteine inco rporation is similar in selenium-replete conditions but, when selenium is limiting, the 3' UTR of cGSH-Px is less efficient than the 3' UTR of PHGSH-Px. The results suggest that the 3' UTR of these selenoprotei n mRNA species influences their extent of translation when selenium le vels are low. The different sensitivity of the 3' UTRs to selenium def iciency can explain the differential effect that selenium deficiency h as on cGSH-Px and PHGSH-Px activity and mRNA levels, stability and tra nslation This might be partly responsible for channelling selenium for synthesis of PHGSH-Px rather than cGSH-Px.