The molecular biology of selenocysteine

Abstract

Selenium is an essential trace element that is incorporated into 25 human proteins as the amino acid selenocysteine (Sec). The incorporation of this amino acid turns out to be a fascinating problem in molecular biology because Sec is encoded by a stop codon, UGA. Layered on top of the canonical translation elongation machinery is a set of factors that exist solely to incorporate this important amino acid. The mechanism by which this process occurs, put into the context of selenoprotein biology, is the focus of this review.

Understanding the Genetic Code

“…Arginine, a strongly hydrophilic residue, and opal (UGA), a chain termination codon, are found within this quadrant (13). Interestingly, however, UGA can also code for amino acids: L-selenocysteine (14,15), L-tryptophan (16), and glycine (17), all semipolar residues (18). One can imagine that the primordial code specified three types of amino acids, one hydrophobic, one hydrophilic, and two semipolar.…”

Beyond the Triplet Code: Context Cues Transform Translation

“…Since then, numerous context-dependent modifiers of termination have been identified. For example, the position of a stop codon relative to other features of an mRNA can commit the mRNA to destruction by nonsense-mediated decay (NMD; reviewed in (Hug et al, 2016)); the highly specific, selenocysteine insertion sequence (SECIS)-dependent insertion of the amino acid selenocysteine at a stop codon (reviewed in (Baranov et al, 2015; Gonzalez-Flores et al, 2013)) allows production of full-length, functional proteins from coding regions that use them; and readthrough, in which termination at the stop codon yields wild-type protein and translation through the stop codon yields an extended protein isoform that my have altered or even opposite function (Figure 4A; (Baranov et al, 2015; Eswarappa and Fox, 2015; Steneberg et al, 1998)). While the mechanisms and significance of NMD and selenocysteine insertion are largely established, with few exceptions the causes and consequences of readthrough remain enigmatic.…”

Subcellular Localization of Glutathione Peroxidase, Change in Glutathione System during Ageing and Effects on Cardiometabolic Risks and Associated Diseases

“…It is for this reason that the expression of GPx1 and GPx3 is highly reactive to the deficiency in Se. The basic mechanisms of the synthesis and insertion of Sec in proteins, their characterization, the molecular and physiological functions of selenoproteins, and their roles in human health were reviewed by Vyacheslav [46].…”