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

POST-TRANSCRIPTIONAL CONTROLS
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apolipoprotein B gene
DNA
5′
3′
CAA
TAA
Figure 7–61 C-to-U RNA editing
produces a truncated form of
apolipoprotein B.
no editing editing, CAA UAA
mRNA CAA
UAA
mRNA UAA UAA
new stop codon
protein
protein
protein made in liver
protein made in intestine
produces a shorter form of the protein. In cells of the liver, the editing enzyme is
not expressed, and the full-length apolipoprotein B is produced. The two protein
isoforms have different properties, MBoC6 and n7.980/7.62
each plays a role in lipid metabolism that
is specific to the organ that produces it (Figure 7–61).
Why RNA editing exists at all is a mystery. One idea is that it arose in evolution
to correct “mistakes” in the genome. Another is that it arose as a somewhat slapdash
way for the cell to produce subtly different proteins from the same gene. A
third possibility is that RNA editing originally evolved as a defense mechanism
against retroviruses and retrotransposons and was later adapted by the cell to
change the meanings of certain mRNAs. Indeed, RNA editing still plays important
roles in cell defense. Some retroviruses, including HIV, are extensively edited after
they infect cells. This hyperediting creates many harmful mutations in the viral
RNA genome and also causes viral mRNAs to be retained in the nucleus, where
they are eventually degraded. Although some modern retroviruses protect themselves
against this defense mechanism, RNA editing presumably helps to hold
many viruses in check.
RNA Transport from the Nucleus Can Be Regulated
It has been estimated that in mammals only about one-twentieth of the total mass
of RNA synthesized ever leaves the nucleus. We saw in Chapter 6 that most mammalian
RNA molecules undergo extensive processing and that the “leftover” RNA
fragments (excised introns and RNA sequences 3ʹ to the cleavage/poly-A site) are
degraded in the nucleus. Incompletely processed and otherwise damaged RNAs
are also eventually degraded as part of the quality control system for RNA production.
As described in Chapter 6, the export of RNA molecules from the nucleus is
delayed until processing has been completed. However, mechanisms that deliberately
override this control point can be used to regulate gene expression. This
strategy forms the basis for one of the best-understood examples of regulated
nuclear transport of mRNA, which occurs in the human AIDS virus, HIV.
As we saw in Chapter 5, HIV, once inside the cell, directs the formation of a
double-stranded DNA copy of its genome, which is then inserted into the genome
of the host (see Figure 5–62). Once inserted, the viral DNA can be transcribed as
one long RNA molecule by the host cell’s RNA polymerase II. This transcript is
then spliced in many different ways to produce over 30 different species of mRNA,
which in turn are translated into a variety of different proteins (Figure 7–62). In
order to make progeny virus, entire, unspliced viral transcripts must be exported
from the nucleus to the cytosol, where they are packaged into viral capsids and
serve as the viral genome. This large transcript, as well as alternatively spliced
HIV mRNAs that the virus needs to move to the cytoplasm for protein synthesis,
still carries complete introns. The host cell’s normal block to the nuclear export of
unspliced RNAs therefore presents a special problem for HIV.