Selenocysteine and pyrrolysine incorporation represent
Selenocysteine and pyrrolysine incorporation exemplify programmed recoding events where stop codons acquire sense meaning through dedicated cis-elements and trans-factors rather than translational errors. Mechanisms involve competition with release factors RF1, RF2, eRF1, specialized tRNAs bearing UCA or CUA anticodons, unique elongation factors SelB, EFSec, and orthogonal synthetases PylRS plus mRNA signals SECIS or PYLIS. Recoding preserves genome-wide termination fidelity while permitting selective reassignment at specific loci. This represents evolutionary flexibility of genetic code, not frameshift, misincorporation, or post-translational modification. Such natural code expansion inspired synthetic biologists to engineer additional noncanonical amino acids expanding protein chemistry beyond twenty encoded residues naturally.
Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 6: Stop Codon Recoding as Genetic Code Expansion