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. 2020 Jul 29;33(7):481–497. doi: 10.1089/ars.2020.8097

FIG. 1.

FIG. 1.

Pathway of selenocysteine synthesis and its incorporation into selenoproteins. Sec is synthesized on its own tRNA (tRNA[Ser]Sec), which undergoes maturation through sequential modifications, with initial attachment of serine by SARS resulting in Ser-tRNA[Ser]Sec. Subsequent phosphorylation of this serine residue by PSTK generates O-Phosphoseryl-tRNA[Ser]Sec. Finally, SEPSECS catalyzes the acceptance of a selenophosphate, generated from selenide and ATP by SEPHS2, resulting in Sec-tRNA[Ser]Sec. An intermediate complex that includes Sec-tRNA[Ser]Sec, TRNAU1AP, and EEFSEC is subsequently formed. This complex is guided by an interaction with SECISBP2 to the SECIS-element of selenoprotein mRNA, ready for incorporation into the nascent polypeptide. Other factors (ribosomal protein L30, eukaryotic initiation factor eIF4a3, nucleolin, …) also have regulatory roles and influence the Sec insertion process. EEFSEC, Sec tRNA-specific eukaryotic elongation factor; mRNA, messenger RNA; PSTK, phosphoseryl-tRNA kinase; SARS, seryl-tRNA synthetase; Sec, selenocysteine; SECIS, SEleniumCysteine Insertion Sequence; SECISBP2, SECIS binding protein 2; SEPHS2, selenophosphate synthetase 2; SEPSECS, O-phosphoserine tRNA:Sec tRNA synthase; tRNA, transfer RNA; TRNAU1AP, tRNA selenocysteine 1 associated protein 1. Color images are available online.