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Expanding the genetic code--TSRI scientists synthesize 21-amino-acid bacterium

x, called the ribosome, into a protein. The ribosome requires the help of transfer RNA molecules (tRNA) that have been "loaded" with an amino acid, and that requires the help of a "loading" enzyme.

Each tRNA recognizes one specific three-base combination, or "codon," on the mRNA and gets loaded with only the one amino acid that is specific for that codon.

During protein synthesis, the tRNA specific for the next codon on the mRNA comes in loaded with the right amino acid, and the ribosome grabs the amino acid and attaches it to the growing protein chain.

The redundancy of the genetic code comes from the fact that there are more codons than there are amino acids used. In fact, there are 4x4x4 = 64 different possible ways to make a codon--or any three-digit combination of four letters (UAG, ACG, UTC, etc.). With only 20 amino acids used by the organisms, not all of the codons are theoretically necessary.

But nature uses them anyway. Several of the 64 codons are redundant, coding for the same amino acid, and three of them are nonsense codons--they don't code for any amino acid at all. These nonsense codons are useful because normally when a ribosome that is synthesizing a protein reaches a nonsense codon, the ribosome dissociates from the mRNA and synthesis stops. Hence nonsense codons are also referred to as "stop" codons. One of these, called the amber stop codon, UAG, played an important role in Schultz's research.

Schultz knew that if he could provide his cells with what is known as an amber suppressor--a tRNA molecule that recognizes UAG--and also with an enzyme that loaded the amber suppressor tRNA with an unusual amino acid, then he would have a way to site-specifically insert the unusual amino acid into any protein he wanted.

With this system, a ribosome that was reading an mRNA would insert the unusual amino acid when it encountered UAG. Furthermore, any codon in an mRNA that is switched to UAG will encode fo
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Contact: Jason Bardi
jasonb@scripps.edu
858-784-9254
Scripps Research Institute
14-Jan-2003


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