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
413
DNA
METHYLATION
(A)
DNA METHYLATION
unmethylated
DNA region
methylated DNA region
NEW DNA
METHYLATION
STATE
INHERITED
HISTONE
MODIFICATION
EPIGENETIC MECHANISMS THAT ACT IN CIS
HISTONE MODIFICATION
active chromatin
inactive chromatin
NEW
CHROMATIN
STATE
INHERITED
Figure 7–53 Four distinct mechanisms
that can produce an epigenetic
form of inheritance in an organism.
(A) Epigenetic mechanisms that act
in cis. As discussed in this chapter, a
maintenance methylase can propagate
specific patterns of cytosine methylation
(see Figure 7–44). As discussed in
Chapter 4, a histone modifying enzyme
that replicates the same modification that
attracts it to chromatin can result in the
modification being self-propagating (see
Figure 4–44). (B) Epigenetic mechanisms
that act in trans. Positive feedback loops,
formed by transcriptional regulators are
found in all species and are probably the
most common form of cell memory. As
discussed in Chapter 3, some proteins
can form self-propagating prions (Figure
3–33). If these proteins are involved in gene
expression, they can transmit patterns of
gene expression to daughter cells.
(B)
POSITIVE
FEEDBACK
LOOP
ACTIVATED
A
A
A
A
protein A
not made
protein A made
POSITIVE FEEDBACK LOOP BY
TRANSCRIPTION REGULATOR
NEW GENE
EXPRESSION
PATTERN
INHERITED
CONFORMATION
CHANGE TO
AGGREGATED
STATE
EPIGENETIC MECHANISMS THAT ACT IN TRANS
normal folded
protein
PROTEIN AGGREGATION STATE
misfolded protein (prion)
NEW PROTEIN
CONFORMATION
STATE
INHERITED
POSSIBLE
ATTENUATION
CAPPING
SPLICING
AND 3′-END
CLEAVAGE
POSSIBLE
RNA EDITING
NUCLEAR
EXPORT
START RNA
TRANSCRIPTION
RNA
transcript
aborts
nonfunctional
mRNA
sequences
retention and
degradation
in nucleus
Summary
Eukaryotic cells can use inherited forms of DNA methylation and inherited states
of chromatin condensation as additional mechanisms for generating cell memory
of gene expression patterns. An especially dramatic case that involves chromatin
condensation is the inactivation of an entire X chromosome in female mammals.
DNA methylation underlies the phenomenon in mammals of genomic imprinting,
in which the expression of a gene depends on whether it was inherited from the
mother or the father.
MBoC6 m7.445/7.54
POST-TRANSCRIPTIONAL CONTROLS
In principle, every step required for the process of gene expression can be controlled.
Indeed, one can find examples of each type of regulation, and many genes
are regulated by multiple mechanisms. As we have seen, controls on the initiation
of gene transcription are a critical form of regulation for all genes. But other controls
can act later in the pathway from DNA to protein to modulate the amount
of gene product that is made—and in some cases, to determine the exact amino
acid sequence of the protein product. These post-transcriptional controls, which
operate after RNA polymerase has bound to the gene’s promoter and has begun
RNA synthesis, are crucial for the regulation of many genes.
In the following sections, we consider the varieties of post-transcriptional regulation
in temporal order, according to the sequence of events that an RNA molecule
might experience after its transcription has begun (Figure 7–54).
SPATIAL
LOCALIZATION
IN CYTOPLASM
START
TRANSLATION
POSSIBLE
TRANSLATIONAL
RECODING
POSSIBLE
RNA
STABILIZATION
CONTINUED
PROTEIN SYNTHESIS
translation
blocked
RNA degraded
Figure 7–54 Post-transcriptional
controls of gene expression. The final
synthesis rate of a protein can, in principle,
be controlled at any of the steps listed in
capital letters. In addition, RNA splicing,
RNA editing, and translation recoding can
also alter the sequence of amino acids in
a protein, making it possible for the cell to
produce more than one protein variant from
the same gene. Only a few of the steps
depicted here are likely to be critical for the
regulation of any one particular protein.