Selenium is an essential micronutrient which plays different roles in live organisms. The biological effects of selenium are largely mediated by selenoproteins, that contain at least one selenium-containing amino acid, selenocysteine (Sec, U). Sec is described as the 21st naturally occurring amino acid in the genetic code.[1,2]
Selenoproteins occur in organisms representing the three domains of life as well as viruses. It is known that approximately half of eukaryotes have them while only about 25% of bacteria and 15% of archea have conserved these proteins during evolution. Eukaryotes have highly variable sets of selenoproteins (selenoproteomes) that show a mosaic occurrence with some organisms, such vertebrates and algae, having dozens of these proteins whereas other organisms, such as higher plants and fungy, having lost all of them during evolution. In the ones that do not posses selenoproteïns, cysteine-containing homologs of some selenoproteins are utilized instead. The only structural difference between selenocystein and cysteine (Cys) is the presence of a selenium atom instead of a sulphur radical. [1,2,3]
However, it has been reported a higher effectiveness in catalysis that would explain why a large number of organisms have developed and conserved Se-dependent pathways and the specialized machinery required for Se insertion into proteins. Selenoproteins are mostly involved in oxidation-reduction reactions.
After sequencing selenoprotein genes, it was discovered that Sec is encoded by the usually-known stop codon TGA meaning that UGA directs its insertion and requires the presence of a conserved stem-loop structure known as the Sec insertion sequence (SECIS) element.[1,2,3]
Owing to fast development of sequencing methods and genomic tools, new organisms are being genotyped constantly. There is the need to well-annotate its selenoproteome in order to provide a wide and accurate information about phylogenetic evolution.
Synthesis of selenoproteins
The introduction of Sec into proteins require several genes and a complex machinery. In eukariotes, that control of selenoprotein expression at the level of the UGA-selenocysteine recoding process is possible due to a set of dedicated cis-acting factors (the SECIS element and the in-farme UGA codon), trans-acting factors (SPS1,SPS2, SecS, Pstk, eEFsec, SBP2 and the tRNA[Ser]Sec) as well as a variety of regulatory mechanisms and elements, that enables a high grade of translational control. 
The incorporation of Sec is dictated by the UGA codon, as previously described. This represents a challenge for the ribosome because UGA is usually a termination signal. [2,4]
The genetic code illustrating the dual function of the UGA codon and that Sec is the 21st amino acid that is encoded by UGA. (Labunskyy VM, et al. 2014)
Fortunately, there are three unique aspects of selenoprotein mRNA translation that enable the clarification of this duality:
- Sec is an amino acid synthesized on its tRNA
- Decodification of UGA as Sec depends on the cis- elements
- Standard elongation factors do not recognise the mRNA and Sec-tRNASec is delivered to the ribosome by trans-acting proteins
Scheme of the Se-proteins biosynthesis pathway.(Roman M, et al. 2014)
Interestingly, Sec is the only aminoacid synthesized directly on the tRNA, and isn’t produced from a cysteine but from a serine[5,6]. tRNA Pstk phosphorylates the tRNA[Ser]Sec , which will allow the next reaction. Selenophosphate synthetase 2 SPS2 prepares the Selenium to be incorporated, and selenocysteine synthase (SecS) binds the atom to the serine, completing the synthesis of the tRNA. This tRNA is not recognized by usual elongation factors, and is instead bound to the specific factor eEFSec.[5,7,8]
tRNA Selenocysteine 1 associated protein 1 (Secp43) is also involved in the synthesis of the tRNA[Ser]Sec and selenoproteins.
Mechanism of Sec insertion in eukaryotes.(Labunskyy VM, et al. 2014)
At this point, the selenocysteine insertion sequence (SECIS) element within selenoprotein mRNA, which is a conserved stem-loop structure encoded in the 3’-UTR of the selenoprotein mRNA in eukaryotes, plays an important role in order to recodify the UGA codon. [5,6]
The protein SBP2 (SECIS Binding Protein 2), that is stably associated with ribosomes, binds the 3D SECIS structure and allows the recruitment of the eEFSec that reclutes the tRNAsec. This is essentialy needed because this specific tRNA is not recognized by typical elongation factors. The incorporation of the selenocysteine residue into the growing polypeptide occurs because the tRNA[Ser]Sec has an anticodon complementary to the UGA. After that, the decoding process continues to complete the selenoprotein translation.[5,9]
There are other proteins that play a role in selenoproteins biosynthesis such as the ribosomal protein L30, which is part of the basal Sec insertion machinery; nucleolin and eIF4A3, that are regulatory proteins.