3'-Untranslated regions are important in mRNA localization and translation: lessons from selenium and metallothionein.

There is increasing evidence that 3'-UTRs (3'-untranslated regions) of mRNAs contain regulatory elements that have important roles in post-transcriptional control of gene expression. For example, 3'-UTRs are important in determining mRNA localization and directing selenocysteine insertion during selenoprotein synthesis. Metallothionein mRNA is localized around the nucleus and associated with the cytoskeleton; this is determined by the 3'-UTR. Deletion and mutagenesis studies are defining the nature of the signal. Incorrect mRNA localization prevents subsequent nuclear localization of metallothionein protein and affects its function. Selenium (Se) is incorporated as selenocysteine into approx. 30 mammalian proteins by a mechanism that requires a specific structure within the 3'-UTR of the corresponding mRNAs. When Se supply is low the effect on selenoprotein expression is not uniform but shows differential effects that are tissue- and protein-specific; there is a 'prioritization' of selenoprotein synthesis that is partly influenced by the 3'-UTRs of the different mRNAs. Single-nucleotide polymorphisms in the gene regions corresponding to 3'-UTRs could potentially influence gene regulation. We have discovered a common polymorphism in a part of the glutathione peroxidase 4 gene which corresponds to the 3'-UTR, and our recent results suggest that this single-nucleotide polymorphism has functional and physiological effects, as well as altered frequency in disease.