Stimulation of stop codon readthrough: frequent presence of an extended 3' RNA structural element

Firth, Andrew E.; Wills, Norma M.; Gesteland, Raymond F.; Atkins, John F.

There are two types of exceptions to universality of the genetic code. In one, the meaning of a codon is globally reassigned in a context independent manner (1) . In the other, codon redefinition is in competition with standard decoding and it is codon context dependent (2) . Though there is an example where the meaning of a sense codon is redefined (3) , most cases of codon redefinition involve one of the three stop codons of the standard code (UGA, UAG or UAA) specifying an amino acid at least a proportion of the time that it is decoded. Where the significant feature of stop codon redefinition is to allow ribosomes to continue translation into a downstream open reading frame (ORF), rather than the identity of the amino acid specified, then it is generally termed stop codon readthrough (RT) (4) . In contrast, when selenocysteine or pyrrolysine are specified by UGA or UAG, respectively, then the important features are the special properties of these non-universal amino acids (5) (6) (7) . Both types of non-global codon redefinition are just one aspect of the variety of ways (collectively referred to as 'recoding') in which genetic readout can be dynamically altered in a site-or mRNA-specific manner (8, 9) .