Selenoprotein synthesis machinery

The selenoprotein synthesis machinery is a specialized biological system required for the recoding of the UGA stop codon to specify the insertion of selenocysteine, the 21st amino acid (Labunskyy et al., 2014). This complex process involves several key components, including the selenocysteine-specific tRNA (tRNA[Ser]Sec), the SECIS-binding protein 2 (SECISBP2), and the selenocysteine-specific elongation factor (EEFSEC) (Squires & Berry, 2008). These components recognize the Selenocysteine Insertion Sequence (SECIS) element in the 3' untranslated region of selenoprotein mRNAs to facilitate proper translation (Papp et al., 2007). Enzymes such as selenophosphate synthetase 2 (SEPHS2) and O-phosphoseryl-tRNA(Sec) selenium transferase (SEPSECS) are also essential for the biosynthesis of the selenocysteine residue itself (Xu et al., 2007). Selenoproteins produced by this machinery, such as glutathione peroxidases and thioredoxin reductases, are vital for maintaining cellular redox balance and protecting against oxidative damage (Reeves & Hoffmann, 2009). Dysfunction in this machinery is associated with various diseases, including Keshan disease, thyroid dysfunction, and increased cancer susceptibility (Bellinger et al., 2009). In oncology, the machinery is often upregulated to protect cancer cells from high levels of reactive oxygen species, making it a potential target for therapeutic inhibition (Carlson et al., 2010). Conversely, selenium supplementation is used to support the machinery's function in populations with selenium deficiency to prevent cardiovascular and immune-related pathologies (Rayman, 2012).

Other names

Selenocysteine biosynthetic pathwaySelenocysteine insertion machinerySECIS-dependent translation machinerySelenoprotein translation machinery

Provision of selenium as a substrate for selenophosphate synthesis; competitive inhibition of selenocysteine incorporation; pharmacological mimicry of selenoprotein activity.