Role of the 3' untranslated region in the regulation of cytosolic glutathione peroxidase and phospholipid-hydroperoxide glutathione peroxidase gene expression by selenium supply.
Selenium is an essential nutrient and synthesis of selenoproteins is affected by limited selenium supply. During selenium deficiency there is a differential regulation of selenoprotein synthesis and gene expression; for example, there is a decrease in abundance of mRNA for cytosolic glutathione peroxidase (cGSH-Px) and a preservation of mRNA for phospholipid-hydroperoxide glutathione peroxidase (PHGSH-Px). This difference is not due to an alteration in the rate of transcription but might reflect differences in translation. The aim of the present work was to assess the role of cGSH-Px and PHGSH-Px 3' untranslated regions (UTRs) in the regulation of selenoprotein mRNA stability and translation by using H4-II-E-C3 cells transfected with different constructs containing a type I iodothyronine deiodinase-coding region linked to different selenoprotein mRNA 3' UTRs. Translational efficiency results showed that the efficiency of the 3' UTRs in permitting selenocysteine incorporation 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 selenoprotein mRNA species influences their extent of translation when selenium levels are low. The different sensitivity of the 3' UTRs to selenium deficiency can explain the differential effect that selenium deficiency has on cGSH-Px and PHGSH-Px activity and mRNA levels, stability and translation. This might be partly responsible for channelling selenium for synthesis of PHGSH-Px rather than cGSH-Px.
Bermano
G
G
Division of Biochemical Sciences, Rowett Research Institute, Bucksburn, Aberdeen, Scotland, U.K.
Arthur
J R
JR
Hesketh
J E
JE
D000818:Animals; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012643:Selenium / Q000172:deficiency / Q000494:pharmacology*; D051140:Selenoproteins; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
D008054:Lipid Peroxides; D010743:Phospholipids; D011506:Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D051140:Selenoproteins; D007453:Iodide Peroxidase; D005979:Glutathione Peroxidase; D012643:Selenium