As discussed in Chapter 1, the genetic code (shown in Figure 6–48) applies to all three major branches of life, providing important evidence for the common ancestry of all life on Earth. Although rare, there are exceptions to this code. For example, Candida albicans, the most prevalent human fungal pathogen, translates the codon CUG as serine, whereas nearly all other organisms translate it as leucine. Mitochondria (which have their own genomes and encode much of their translational apparatus) often deviate from the standard code. For example, in mammalian mitochondria AUA is translated as methionine, whereas in the
Figure 6–72 The final phase of protein synthesis. The binding of a release factor to an A site bearing a stop codon terminates translation. The completed polypeptide is released and, in a series of reactions that requires additional proteins and GTP hydrolysis (not shown), the ribosome dissociates into its two separate subunits.
messenger RNA Figure 6–73 A polyribosome. (A) Schematic drawing showing how a series of ribosomes can simultaneously translate the same eukaryotic mRNA molecule. (B) Electron micrograph of a polyribosome from a eukaryotic cell (Movie 6.10). (B, courtesy of John Heuser.) cytosol of the cell it is translated as isoleucine (see Table 14–3, p. 805). This type of deviation in the genetic code is “hardwired” into the organisms or the organelles in which it occurs.
A different type of variation, sometimes called translation recoding, occurs in many cells. In this case, other nucleotide sequence information present in an mRNA can change the meaning of the genetic code at a particular site in the mRNA molecule. The standard code allows cells to manufacture proteins using only 20 amino acids. However, bacteria, archaea, and eukaryotes have available to them a twenty-first amino acid that can be incorporated directly into a growing polypeptide chain through translation recoding. Selenocysteine, which is essential for the efficient function of a variety of enzymes, contains a selenium atom in place of the sulfur atom of cysteine. Selenocysteine is enzymatically produced from a serine attached to a special tRNA molecule that base-pairs with the UGA codon, a codon normally used to signal a translation stop. The mRNAs for proteins in which selenocysteine is to be inserted at a UGA codon carry an additional nearby nucleotide sequence in the mRNA that triggers this recoding event (Figure 6–74).
added to growing seryl-tRNA converted to selenocysteine selenocysteine tRNA signal that the preceding UGA encodes selenocysteine
Figure 6–74 Incorporation of selenocysteine into a growing polypeptide chain. A specialized tRNA is charged with serine by the normal seryltRNA synthetase, and the serine is subsequently converted enzymatically to selenocysteine. A specific RNA structure in the mRNA (a stem and loop structure with a particular nucleotide sequence) signals that selenocysteine is to be inserted at the neighboring UGA codon. As indicated, this event requires the participation of a selenocysteine-specific translation factor. After the addition of selenocysteine, translation continues until a conventional stop codon is encountered.
Inhibitors of Prokaryotic Protein Synthesis Are Useful as Antibiotics