SecIS

SECIS, short for Selenocysteine Insertion Sequence, is an RNA structural element that enables the reinterpretation of UGA codons from stop signals to encoding the amino acid selenocysteine in a subset of proteins known as selenoproteins. Selenocysteine is the 21st amino acid and contains selenium, inserted cotranslationally at designated UGA sites in the presence of SECIS and the appropriate translation machinery.

The location and mode of action of SECIS elements differ across domains of life. In bacteria, the SECIS element is typically located in the coding region, immediately downstream of the UGA codon, and works with the Sec-specific tRNA (tRNASec) and the GTPase SelB to insert Sec at the UGA site. In archaea and eukaryotes, the SECIS element resides in the 3' untranslated region (3' UTR) of the mRNA and interacts with the Sec insertion machinery, including the SBP2 protein and the elongation factor eEFSec, to recruit Sec-tRNASec to the ribosome.

The incorporation of selenocysteine depends on the availability of selenium and the presence of a functional SECIS element, tRNASec, and the appropriate protein factors. Disruption of SECIS function or selenium supply can impair Sec incorporation and affect the activity of many selenoproteins, such as glutathione peroxidases and thioredoxin reductases, which often participate in redox biology.

SECIS elements are conserved RNA structures with key motifs, yet they exhibit domain-specific variations that reflect differences in the Sec insertion machinery among bacteria, archaea, and eukaryotes. They are essential for organisms that rely on selenoproteins for specific physiological processes.