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 in the mRNA (UAG, ACG, UCC, 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, the amber stop codon UAG, played an important role in Schultz's research.

Schultz and his colleagues knew that if they could provide their cells with a tRNA molecule that recognizes UAG and also provide them with a synthetase "loading" enzyme that loaded the tRNA with an unnatural amino acid, the scientists would have a way to site-specifically insert the unusual amino acid into any protein they wanted.

They needed to find a functionally "orthogonal" paira tRNA/synthetase pair that react with each other but not with endogenous E. coli pairs. So they devised a
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Contact: Jason Bardi
jasonb@scripps.edu
858-784-9254
Scripps Research Institute
11-May-2004