SelenocysteinInsertion

Selenocysteine insertion is the translational recoding process by which the UGA codon is redefined to specify the amino acid selenocysteine (Sec) in response to a SECIS element in the mRNA of certain selenoproteins.

In bacteria, the Sec incorporation pathway uses a dedicated tRNA Sec (encoded by selC) and enzymes SelA (selenocysteine synthase) and SelB (a specialized translation factor) with selenophosphate produced by SelD. Sec-tRNA Sec is delivered to the ribosome at UGA in the presence of the SECIS element.

In archaea and eukaryotes, the tRNA Sec is initially charged with serine by seryl-tRNA synthetase, then phosphorylated by PSTK to Sep-tRNA Sec and converted to Sec-tRNA Sec by SecS, using selenophosphate supplied by SPS. The Sec-tRNA Sec is delivered to the ribosome by the elongation factor specialized for Sec in these organisms.

SECIS elements differ in location and interaction across domains. In bacteria, the SECIS element is typically located within the coding region and interacts with SelB; in eukaryotes and many archaea, the SECIS resides in the 3' untranslated region and is bound by SBP2, with eEFSec delivering Sec-tRNA Sec to the ribosome.

Selenoproteins, which require Sec for catalytic efficiency, include antioxidant enzymes such as glutathione peroxidases and thioredoxin reductases, as well as thyroid hormone–related deiodinases. Sec insertion is selenium-dependent and varies across organisms: some lineages retain a complete Sec system, others retain only parts, and some have lost Sec entirely.