Many of the most effective antibiotics used in modern medicine are compounds made by fungi that inhibit bacterial protein synthesis. Fungi and bacteria compete for many of the same environmental niches, and millions of years of coevolution have resulted in fungi producing potent bacterial inhibitors. Some of these drugs exploit the structural and functional differences between bacterial and eukaryotic ribosomes so as to interfere preferentially with the function of bacterial ribosomes. Thus, humans can take high dosages of some of these compounds without undue toxicity. Many antibiotics lodge in pockets in the ribosomal RNAs and simply interfere with the smooth operation of the ribosome; others block specific parts of the ribosome such as the exit channel (Figure 6–75). Table 6–4 lists some common antibiotics of this kind along with several other inhibitors of protein synthesis, some of which act on eukaryotic cells and therefore cannot be used as antibiotics.
Because they block specific steps in the processes that lead from DNA to protein, many of the compounds listed in Table 6–4 are useful for cell biological studies. Among the most commonly used drugs in such investigations are chloramphenicol, cycloheximide, and puromycin, all of which specifically inhibit protein synthesis. In a eukaryotic cell, for example, chloramphenicol inhibits protein synthesis on ribosomes only in mitochondria (and in chloroplasts in plants), presumably reflecting the prokaryotic origins of these organelles (discussed in Chapter 14). Cycloheximide, in contrast, affects only ribosomes in the cytosol. Puromycin is especially interesting because it is a structural analog of a tRNA molecule linked to an amino acid and is therefore another example of molecular mimicry; the ribosome mistakes it for an authentic amino acid and covalently incorporates it at the C-terminus of the growing peptide chain, thereby causing the premature termination and release of the polypeptide. As might be expected, puromycin inhibits protein synthesis in both prokaryotes and eukaryotes.
Quality Control Mechanisms Act to Prevent Translation of Damaged mRNAs
In eukaryotes, mRNA production involves both transcription and a series of elaborate RNA processing steps; as we have seen, these take place in the nucleus, segregated from ribosomes, and only when the processing is complete are the mRNAs transported to the cytosol to be translated (see Figure 6–38). However, this scheme is not foolproof, and some incorrectly processed mRNAs are inadvertently sent to the cytosol. In addition, mRNAs that were flawless when they left the nucleus can become broken or otherwise damaged in the cytosol. The danger of