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  Topic: Stop codon thievery< Next Oldest | Next Newest >  

Posts: 4
Joined: May 2002

(Permalink) Posted: May 30 2002,08:41   

A very recent example of a "stop" codon being
sometimes coopted for another use is the subject of two papers and a "perspective" (1-3) in the 24 May 2002 issue of Science. These all are reporting on the "new" amino acid "pyrrolysine", which is coded for by the (usually) stop codon UAG in a certain methanogenic archaeon's mRNA. To quote from (1):

The way in which pyrrolysine is encoded bears striking parallels to the encoding of the 21st amino acid, selenocysteine. Selenocysteine is found in Archaea, eubacteria and animals, including mammals . Both nonstandard amino acids are encoded by the RNA nucleotide triplets (codons) that signify a command to stop translation of mRNA into protein (UGA is the "stop codon" encoding selenocysteine). The notion that at least 22 amino acids are directly encoded by the nucleotide sequence of mRNA reflects the greater richness of the genetic code than is apparent from the standard textbook account.

Originally, the coding problem was defined in terms of how the 20 common amino acids could be specified by four RNA nucleotides. As the triplet nature of the genetic code began to unfold in the early 1960s, it might have been tempting to speculate that some of the 64 possible codons encoded the many rare amino acids found in proteins. However, it became clear that 20 is the correct number of amino acids, and that the great majority of nonstandard amino acids are created by chemical modifications of standard amino acids after translation. In 1986 came the surprise discovery that the nonstandard amino acid selenocysteine is directly specified by the genetic code and is not created by posttranslational modification. Selenocysteine is now joined by pyrrolysine, and together these two amino acids demonstrate that the genetic code can be expanded by redefining the meaning of a stop codon.   {references omitted}

Reference (1) goes into some depth, with references, as to how the stop signal is subverted in the case of selenocysteine, the only other non-canonical amino acid known to be specified by the code and not built by modification after translation. In the selenocysteine case, only a minority of the UGA codons are used to code the amino acid: most are still stop codons. Signals elsewhere in the mRNA determine which. It is still unknown just hoe the UAG coding pyrrolysine works, however.

(1) Atkins JF, Gesteland R. Science 2002 May 24;296(5572):1409-10
(2) G. Srinivasan et al., Science 296, 1459 (2002).
(3) B. Hao et al., Science 296, 1462 (2002).

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