Molecular Genetics 

Facts

• Several enzymes (for example, glutathione peroxidase, tetraikiodothyronine 5' deiodinase and formate dehydrogenase) contain the unusual amino acid selenocysteine. 
• The genes for glutathione peroxidase and formate dehydrogenase contain TGA codons in the middle of their coding regions (ref). The TGA follows the codon for the amino acid that precedes the selenocysteine in the polypeptide chain.
• In the absence of selenium, protein synthesis from these mRNAs terminates prematurely.
• Mutations at four distinct loci selectively prevent the formation of selenocysteine-containing enzymes (ref). The functions of the four genes have been worked out (see Table).
• In the formate dehydrogenase mRNA, a region 40 bp downstream of the UGA codon is also needed for selenocysteine incorporation (ref).
• In the tetraikiodothyronine 5' deiodinase mRNA, a 250 bp region in the 3' untranslated region (about 1 kbp removed from the UGA) is also required for selenocysteine incorporation (ref).

Interpretations

• In a limited number of genes, a special UGA codon, normally a termination codon, is used as a codon for the unusual amino acid selenocysteine (ref).
• Sequences additional to UGA are part of the signal for selenocysteine incorporation. The placement of the additional signal is variable.
• The triplet genetic code is not the sole determinant of amino acid sequence.
• A serRS aminoacylates the selC product with serine.  The seryl moiety is converted to the dehydroalanyl moiety by the selA product.  Activated selenium adds to the dehydroalanine to form selenocysteine.

Further information  

• Selenoprotein-P contains multiple (7 to 10) selenocysteine residues (ref). Stem-loop structures are responsible for selenocysteine insertion (ref).
• In eucaryotes, a protein that binds specifically to SECIS elements, SBP2, also plays a role in selenocysteine incorporation (rev)
• Data suggest that once a ribosome has incorporated selenocysteine at the first UGA rather than stopping, it will also put selenocysteine in in response to other UGA codons (rev).
• Selenocysteinyl tRNA may compete directly with release factor 2 for binding to the P site of the ribosome (ref).
• SECIS contains a K-turn structure.
• tRNASec has unusual features compared to other tRNAs (ref1; ref2): It is thought that these features prevent it interacting with the predominant EFTu.
  • a 6 bp D-loop stem with a 4 bp loop;
  • an extended acceptor stem-T stem axis of 13 bp
  • a large extra arm.
• In some archaebacteria, the amino acid pyrrolysine is charged directly to a tRNA with a CUA anticodon (ref). The pyrrolysine is subsequently incorporated into some proteins in response to a UAG codon.

This is page 2411 of Molecular Genetics by Ulrich Melcher, © 1997, 1998, 2002, 2004