Recent Developments in (Archaeal) Pyrrolysine and Selenocysteine Specification and Metabolism

Although many naturally occurring modified amino acids have been identified in living organisms, only two, selenocysteine and pyrrolysine, are genetically encoded. Each amino acid is inserted cotranslationally into proteins imparting catalytic functionality. Both selenocysteine and pyrrolysine are encoded in genes by what are otherwise stop codons. The 2 aa contrast in how they are biosynthesized. Selenocysteine is synthesized on the dedicated tRNA^Sec following serylation by seryl-tRNA synthetase. Pyrrolysine is made as a free amino acid and then used to aminoacylate its specific tRNA^Pyl by pyrrolysyl-tRNA^Pyl synthetase. The 2 aa further differ in how message context influences translation. Translation of UGA as selenocysteine relies heavily on the presence of a specific messenger RNA (mRNA) sequence found in the transcript. In contrast, local message context stimulates, but is not required for, relatively efficient translation of UAG as pyrrolysine.