Understanding selenoprotein function and regulation through the use of rodent models

Abstract

Selenium (Se) is an essential micronutrient. Its biological functions are associated with selenoproteins, which contain this trace element in the form of the 21st amino acid, selenocysteine. Genetic defects in selenocysteine insertion into proteins are associated with severe health issues. The consequences of selenoprotein deficiency are more variable, with several selenoproteins being essential, and several showing no clear phenotypes. Much of these functional studies benefited from the use of rodent models and diets employing variable levels of Se. This review summarizes the data obtained with these models, focusing on mouse models with targeted expression of individual selenoproteins and removal of individual, subsets or all selenoproteins in a systemic or organ-specific manner. This article is part of a Special Issue entitled: Cell Biology of Metals.

Figure 1. Mechanisms of eukaryotic Sec biosynthesis and incorporation

Sec tRNA^[Ser]Sec is initially charged with Ser, which is further phosphorylated by PSTK. SPS2 facilitates the synthesis of selenophosphate, the selenium donor compound. SecS then catalyzes Sec formation. SECp43 may be involved in the methylation of Sec tRNA^[Ser]Sec at the A34 position. Protein factors, including SBP2 and EFSec, bind the SECIS element, located in the 3’-UTRs of selenoprotein mRNAs. After translocation to the cytosol, protein factors support interaction with the ribosome and Sec incorporation.