Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

352 Chapter 6: How Cells Read the Genome: From DNA to Protein
Table 6–4 Inhibitors of Protein or RNA Synthesis
Inhibitor
Specific effect
Acting only on bacteria
Tetracycline
Streptomycin
Blocks binding of aminoacyl-tRNA to the A site of ribosome
Prevents the transition from translation initiation to chain elongation and also causes miscoding
Chloramphenicol Blocks the peptidyl transferase reaction on ribosomes (step 2 in Figure 6–64)
Erythromycin
Rifamycin
Binds in the exit channel of the ribosome and thereby inhibits elongation of the peptide chain
Blocks initiation of RNA chains by binding to RNA polymerase (prevents RNA synthesis)
Acting on bacteria and eukaryotes
Puromycin
Actinomycin D
Causes the premature release of nascent polypeptide chains by its addition to the growing chain end
Binds to DNA and blocks the movement of RNA polymerase (prevents RNA synthesis)
Acting on eukaryotes but not bacteria
Cycloheximide Blocks the translocation reaction on ribosomes (step 3 in Figure 6–64)
Anisomycin Blocks the peptidyl transferase reaction on ribosomes (step 2 in Figure 6–64)
α-Amanitin
Blocks mRNA synthesis by binding preferentially to RNA polymerase II
The ribosomes of eukaryotic mitochondria (and chloroplasts) often resemble those of bacteria in their sensitivity to inhibitors. Therefore, some of
these antibiotics can have a deleterious effect on human mitochondria.
translating damaged or incompletely processed mRNAs (which would produce
truncated or otherwise aberrant proteins) is apparently so great that the cell has
several backup measures to prevent this from happening. To avoid translating
broken mRNAs, for example, the 5ʹ cap and the poly-A tail are both recognized by
the translation-initiation machinery before translation begins (see Figure 6–70).
The most powerful mRNA surveillance system, called nonsense-mediated
mRNA decay, eliminates defective mRNAs before they move away from the
nucleus. This mechanism is brought into play when the cell determines that an
mRNA molecule has a nonsense (stop) codon (UAA, UAG, or UGA) in the “wrong”
place. This situation is likely to arise in an mRNA molecule that has been improperly
spliced, because aberrant splicing will usually result in the random introduction
of a nonsense codon into the reading frame of the mRNA—especially
in organisms, such as humans, that have a large average intron size (see Figure
6–31B).
The nonsense-mediated mRNA decay mechanism begins as an mRNA molecule
is being transported from the nucleus to the cytosol. As its 5ʹ end emerges
from a nuclear pore, the mRNA is met by a ribosome, which begins to translate
it. As translation proceeds, the exon junction complexes (EJCs) that are bound
to the mRNA at each splice site are displaced by the moving ribosome. The normal
stop codon will lie within the last exon, so by the time the ribosome reaches
it and stalls, no more EJCs will be bound to the mRNA. In this case, the mRNA
“passes inspection” and is released to the cytosol where it can be translated in earnest
(Figure 6–76). However, if the ribosome reaches a stop codon earlier, when
EJCs remain bound, the mRNA molecule is rapidly degraded. In this way, the first
round of translation allows the cell to test the fitness of each mRNA molecule as it
exits the nucleus.
Nonsense-mediated decay may have been especially important in evolution,
allowing eukaryotic cells to more easily explore new genes formed by DNA rearrangements,
mutations, or alternative patterns of splicing—by selecting only those
mRNAs for translation that can produce a full-length protein. Nonsense-mediated
decay is also important in cells of the developing immune system, where
the extensive DNA rearrangements that occur (see Figure 24–28) often generate