Translation of UAG as Pyrrolysine

  • Joseph A. Krzycki
Part of the Nucleic Acids and Molecular Biology book series (NUCLEIC, volume 24)


Pyrrolysine followed selenocysteine in order of discovery. While both atypical amino acids are encoded by canonical stop codons, the mechanisms by which they are inserted into protein are very different. Pyrrolysine is carried to the ribosome by tRNAPyl (encoded by pylT) whose unusual structure possesses the CUA anticodon needed to decode UAG. A pyrrolysyl-tRNA synthetase (product of pylS) ligates pyrrolysine to tRNAPyl. Pyrrolysine is made by the products of the pylBCD genes without the need for tRNAPyl, contrasting with selenocysteine synthesis on tRNASec. Isolated examples of the pylTSBCD genes, often in a single cluster, have been found in genomes of methanogenic Archaea, G+ Bacteria, and δ-proteobacteria. Escherichia coli transformed with pyl genes translates UAG as endogenously synthesized pyrrolysine. The ease of the lateral transfer of the genetic encoding of pyrrolysine is now being exploited for tailoring recombinant proteins. Pyrrolysine incorporation appears to occur to some extent by amber suppression on a genome-wide basis in methanogenic Archaea. With some methylamine methyltransferase transcripts, a putative pyrrolysine insertion sequence (PYLIS) forms an in-frame stem-loop 3 to the translated UAG, analogous to such loops required in Bacteria for translation of UGA as selenocysteine. PYLIS sequences are not found in all types of methylamine methyltransferases. Unlike the precedent of selenocysteine, after deletion of PYLIS, significant UAG translation remains with a marked increase in UAG-directed termination, suggesting some part of the PYLIS sequence functions in enhancing amber suppression. Some methanogen genomes encode additional homologs of elongation and release factors, however, their limited distribution suggests at best a nonessential role in enhancing UAG translation as pyrrolysine.


Stop Codon Genetic Code Methyltransferase Gene Imine Bond Sense Codon 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Research in the author’s laboratory is supported by the Department of Energy (DEFG020291ER200042) and the National Institute of Health (GM070663).


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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of MicrobiologyThe Ohio State UniversityColumbusUSA

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