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16
Regulation of Gene
Expression
16 Regulation of Gene Expression
16.1 How Is Gene Expression Regulated in
Prokaryotes?
16.2 How Is Eukaryotic Gene Transcription
Regulated?
16.3 How Do Viruses Regulate Their Gene
Expression?
16.4 How Do Epigenetic Changes Regulate
Gene Expression?
16.5 How Is Eukaryotic Gene Expression
Regulated After Transcription?
16 Regulation of Gene Expression
Behavioral epigenetics: study of heritable
changes in gene expression that do not
involve changes in the DNA sequence.
Methylation of some gene promoters may
result from high levels of stress, and inhibit
gene transcription. Methylation in the
glucocorticoid receptor gene may result in
behavioral problems.
Opening Question:
Can epigenetic changes be manipulated?
16.1 How Is Gene Expression Regulated in Prokaryotes?
Prokaryotes can make some proteins only
when they are needed. To shut off
supply of a protein, the cell can:
• Downregulate mRNA transcription
• Hydrolyze mRNA, preventing translation
• Prevent mRNA translation at the
ribosome
• Hydrolyze the protein after it is made
• Inhibit the protein’s function
16.1 How Is Gene Expression Regulated in Prokaryotes?
The earlier the cell can stop protein
synthesis, the less energy is wasted.
Blocking transcription is more efficient
than transcribing the gene, translating
the message, and then degrading or
inhibiting the protein.
16.1 How Is Gene Expression Regulated in Prokaryotes?
Gene expression begins at the
promoter.
Two types of regulatory proteins can
bind to promoters:
• Negative regulation—a repressor
protein prevents transcription
• Positive regulation—an activator
protein stimulates transcription
Figure 16.1 Positive and Negative Regulation
16.1 How Is Gene Expression Regulated in Prokaryotes?
E. coli in the human intestine must
adjust quickly to changes in food
supply.
Glucose is the easiest sugar to
metabolize.
Lactose is β-galactoside
(disaccharide of galactose and
glucose).
16.1 How Is Gene Expression Regulated in Prokaryotes?
Three proteins are need for the uptake
and metabolism of lactose.
• -galactoside permease—carrier
protein that moves lactose into the cell
• -galactosidase—hydrolyses lactose
• -galactoside transacetylase—
transfers acetyl groups from acetyl
CoA to certain -galactosides
16.1 How Is Gene Expression Regulated in Prokaryotes?
If E.coli is grown with glucose but no
lactose, no enzymes for lactose
conversion are produced.
If lactose is predominant and glucose is
low, E.coli synthesizes all three
enzymes after a short lag period.
Figure 16.2 An Inducer Stimulates the Expression of a Gene for an Enzyme
16.1 How Is Gene Expression Regulated in Prokaryotes?
During the lag period, mRNA for βgalactosidase is produced.
If lactose is removed, the mRNA level
goes down.
16.1 How Is Gene Expression Regulated in Prokaryotes?
Compounds that stimulate protein
synthesis are called inducers;
The proteins are inducible proteins.
Constitutive proteins are made at a
constant rate.
16.1 How Is Gene Expression Regulated in Prokaryotes?
Metabolic pathways can be regulated in
two ways:
• Allosteric regulation of enzymecatalyzed reactions allows rapid finetuning
• Regulation of protein synthesis is
slower but conserves energy and
resources. Protein synthesis requires
a lot of energy
Figure 16.3 Two Ways to Regulate a Metabolic Pathway
16.1 How Is Gene Expression Regulated in Prokaryotes?
Structural genes specify primary
protein structure—the amino acid
sequence.
The 3 structural genes for lactose
enzymes are adjacent on the
chromosome and share a promoter,
forming the lac operon.
16.1 How Is Gene Expression Regulated in Prokaryotes?
An operon is a gene cluster with a
single promoter.
A typical operon consists of:
• A promoter
• Two or more structural genes
• An operator—a short sequence
between the promoter and the
structural genes; binds to regulatory
proteins
Figure 16.4 The lac Operon of E. coli
16.1 How Is Gene Expression Regulated in Prokaryotes?
Three ways to control operon
transcription:
• An inducible operon regulated by a
repressor protein
• A repressible operon regulated by a
repressor protein
• An operon regulated by an activator
protein
16.1 How Is Gene Expression Regulated in Prokaryotes?
In the lac operon the operator can bind
a repressor protein, which blocks
transcription.
The repressor has 2 binding sites: one
for the operator, and one for the
inducer (lactose).
When lactose is absent, the repressor
prevents binding of RNA polymerase
to the promoter.
Figure 16.5 The lac Operon: An Inducible System (Part 1)
16.1 How Is Gene Expression Regulated in Prokaryotes?
When lactose is present, it binds to the
repressor and changes the
repressor’s shape.
This prevents the repressor from
binding to the operator, and then RNA
polymerase can bind to the promoter,
and the genes are transcribed.
Figure 16.5 The lac Operon: An Inducible System (Part 2)
16.1 How Is Gene Expression Regulated in Prokaryotes?
Other E. coli systems are repressible—
the operon is turned on unless
repressed under specific conditions.
In these systems, the repressor isn’t
bound to the operator until a corepressor binds to it.
The repressor then changes shape,
binds to the operator, and blocks
transcription.
16.1 How Is Gene Expression Regulated in Prokaryotes?
The trp operon is a repressible system.
The genes code for enzymes that
catalyze synthesis of tryptophan.
When there is enough tryptophan in the
cell, tryptophan binds to the repressor,
which then binds to the operator.
Tryptophan is the co-repressor.
16.1 How Is Gene Expression Regulated in Prokaryotes?
Inducible systems: metabolic substrate
(inducer) interacts with a regulatory
protein (repressor); repressor can’t
bind to operator and transcription
proceeds.
Repressible systems: a metabolic
product (co-repressor) binds to a
regulatory protein, which then binds to
the operator and blocks transcription.
16.1 How Is Gene Expression Regulated in Prokaryotes?
Inducible systems control catabolic
pathways—they are turned on when
substrate is available.
Repressible systems control anabolic
pathways—they are turned on until
product concentration becomes
excessive.
16.1 How Is Gene Expression Regulated in Prokaryotes?
Positive control: an activator protein
can increase transcription.
If glucose and lactose levels are both
high, the lac operon is not transcribed
efficiently.
Efficient transcription requires binding
of an activator protein to its promoter.
16.1 How Is Gene Expression Regulated in Prokaryotes?
If glucose levels are low, a signaling
pathway leads to increased levels of
cyclic AMP.
cAMP binds to cAMP receptor protein
(CRP); conformational change in CRP
allows it to bind to the lac promoter.
CRP is an activator of transcription; its
binding results in more efficient
binding of RNA polymerase and thus
increased transcription.
Figure 16.6 Catabolite Repression Regulates the lac Operon
16.1 How Is Gene Expression Regulated in Prokaryotes?
If glucose is abundant, CRP does not
bind to the lac operon promoter and
efficiency of transcription is reduced.
This is catabolite repression, a
system of gene regulation in which
presence of a preferred energy source
represses other catabolic pathways.
Figure 16.6 Catabolite Repression Regulates the lac Operon
Table 16.1
16.1 How Is Gene Expression Regulated in Prokaryotes?
Promoters bind and orient RNA
polymerase so that the correct DNA
strand is transcribed.
All promoters have consensus
sequences that allow them to be
recognized by RNA polymerase.
Different classes of consensus
sequences are recognized by
regulatory proteins called sigma
factors.
16.1 How Is Gene Expression Regulated in Prokaryotes?
Sigma factors bind to RNA polymerase
and direct it to certain promoters.
Genes for proteins with related
functions may be at different locations
in the genome, but share consensus
sequences and can be recognized by
sigma factors.
16.1 How Is Gene Expression Regulated in Prokaryotes?
Sigma-70 factor is active most of the
time and binds to consensus
sequences of housekeeping genes
(genes normally expressed in actively
growing cells).
Others are activated only under specific
conditions.
16.2 How Is Eukaryotic Gene Transcription Regulated?
In development of multicellular
organisms, certain proteins must be
made at just the right times and in just
the right cells.
The expression of eukaryotic genes
must be precisely regulated.
Regulation can occur at several
different points.
Figure 16.7 Potential Points for the Regulation of Gene Expression (Part 1)
Figure 16.7 Potential Points for the Regulation of Gene Expression (Part 2)
16.2 How Is Eukaryotic Gene Transcription Regulated?
Both prokaryotes and eukaryotes use
DNA-protein interactions and negative
and positive control to regulate gene
expression.
But there are differences, some
dictated by the presence of a nucleus,
which physically separates
transcription and translation.
Table 16.2
16.2 How Is Eukaryotic Gene Transcription Regulated?
Eukaryote promoters contain a
sequence called the TATA box—
where DNA begins to denature.
Promoters also include regulatory
sequences recognized by
transcription factors (regulatory
proteins).
16.2 How Is Eukaryotic Gene Transcription Regulated?
RNA polymerase II can only bind to the
promoter after general transcription
factors have assembled on the
chromosome:
TFIID binds to TATA box; then other
factors bind to form an initiation
complex.
Figure 16.8 The Initiation of Transcription in Eukaryotes (Part 1)
Figure 16.8 The Initiation of Transcription in Eukaryotes (Part 2)
16.2 How Is Eukaryotic Gene Transcription Regulated?
Some regulatory sequences are
common to promoters of many genes,
such as the TATA box.
Some sequences are specific to a few
genes and are recognized by
transcription factors found only in
certain tissues.
These play an important role in cell
differentiation.
16.2 How Is Eukaryotic Gene Transcription Regulated?
Enhancers: regulatory sequences that
bind transcription factors that activate
transcription or increase rate of
transcription.
Silencers: bind transcription factors
that repress transcription.
16.2 How Is Eukaryotic Gene Transcription Regulated?
Most regulatory sequences are located
near the transcription start site.
Others may be located thousands of
base pairs away. Transcription factors
may interact with the RNA polymerase
complex and cause the DNA to bend.
Figure 16.9 Transcription Factors and Transcription Initiation
16.2 How Is Eukaryotic Gene Transcription Regulated?
Often there are many transcription
factors involved.
The combination of factors present
determines the rate of transcription.
Although the same genes are present
in all cells, the fate of the cell is
determined by which of its genes are
expressed.
16.2 How Is Eukaryotic Gene Transcription Regulated?
Transcription factors have common
structural motifs in the domains that
bind to DNA.
A common motif is helix-turn-helix:
16.2 How Is Eukaryotic Gene Transcription Regulated?
For DNA recognition, the structural
motif must:
• Fit into a major or minor groove
• Have amino acids that can project into
interior of double helix
• Have amino acids that can bond with
interior bases
16.2 How Is Eukaryotic Gene Transcription Regulated?
Many repressor proteins, such as the
lac repressor, have helix-turn-helix
motifs:
16.2 How Is Eukaryotic Gene Transcription Regulated?
During development, cell differentiation
is often mediated by changes in gene
expression.
All differentiated cells contain the entire
genome; their specific characteristics
arise from differential gene
expression.
16.2 How Is Eukaryotic Gene Transcription Regulated?
Cellular therapy is a new approach to
diseases that involve degeneration of
one cell type.
Alzheimer’s disease involves
degeneration of neurons in the brain.
If other cells could be made to
differentiate into neurons, they could
be transferred to the patient.
Figure 16.10 Expression of Specific Transcription Factors Turns Fibroblasts into Neurons
16.2 How Is Eukaryotic Gene Transcription Regulated?
How do eukaryotes coordinate
expression of sets of genes?
Most have their own promoters, and
may be far apart in the genome.
If the genes have common regulatory
sequences, they can be regulated by
the same transcription factors.
16.2 How Is Eukaryotic Gene Transcription Regulated?
Plants in drought stress must
synthesize several proteins (the stress
response). The genes are scattered
throughout the genome.
Each of the genes has a regulatory
sequence called stress response
element (SRE). A transcription factor
binds to this element and stimulates
mRNA synthesis.
Figure 16.11 Coordinating Gene Expression
Working with Data 16.1: Expression of Transcription Factors Turns Fibroblasts into Neurons
To determine whether specific
transcription factors might change one
type of cell to another, genes for
transcription factors in neurons were
inserted into fibroblasts.
When five transcription factors were
introduced into fibroblasts and
expressed from very strong
promoters, the fibroblasts became
neurons.
Working with Data 16.1: Expression of Transcription Factors Turns Fibroblasts into Neurons
Three main criteria were used to
determine that the transformed cells
were neurons:
• Morphology
• Electrical excitability
• Lack of cell division
Working with Data 16.1: Expression of Transcription Factors Turns Fibroblasts into Neurons
Question 1:
Neurons respond to electrical stimulation by
generating an action potential. The electrical
activity of a stimulated transformed fibroblast
cell is shown in Fig. A: 8, 12, and 20 days after
addition of the transcription factors.
What is the magnitude of the action potential of
the transformed cell in millivolts?
Look at Figure 45.10. How does this compare?
Working with Data 16.1, Figure A
Figure 45.10 The Course of an Action Potential
Working with Data 16.1: Expression of Transcription Factors Turns Fibroblasts into Neurons
Question 2:
The rate of cell division in the population of
transformed cells was measured by the
incorporation of the labeled nucleotide
BrdU into their DNA.
The percentage of labeled—and hence
dividing—cells is shown in Fig. B.
Did cell division stop in the transformed
cells? Explain your answer.
Working with Data 16.1, Figure B
16.3 How Do Viruses Regulate Their Gene Expression?
Viruses are infectious agents that
infect cellular organisms, and can’t
reproduce outside their host cells.
A bacterial virus (bacteriophage)
injects its genetic material into a host
cell and turns that cell into a virus
factory.
Other viruses enter cells and then shed
their coats and take over the cell’s
replication machinery.
16.3 How Do Viruses Regulate Their Gene Expression?
Virus particles, called virions, consist
of DNA or RNA, a protein coat, and
sometimes a lipid envelope.
Viral genomes contain sequences that
encode regulatory proteins that
“hijack” the host cells’ transcriptional
machinery.
16.3 How Do Viruses Regulate Their Gene Expression?
The viral lytic cycle—host cell lyses
and releases progeny viruses.
A phage injects a host cell with genetic
material that takes over synthesis.
New phage particles appear rapidly
and are soon released from the lysed
cell.
Figure 16.12 Bacteriophage and Host
16.3 How Do Viruses Regulate Their Gene Expression?
The lytic cycle has two stages.
1. Early stage: viral promoter binds
host RNA polymerase. Viral genes
adjacent to this promoter are
transcribed (positive regulation).
16.3 How Do Viruses Regulate Their Gene Expression?
Early genes encode proteins that shut
down host transcription (negative
regulation) and stimulate viral genome
replication and transcription of viral
late genes (positive regulation).
Three minutes after DNA entry, viral
nuclease enzymes digest the host’s
chromosome, providing nucleotides
for the synthesis of viral genomes.
Figure 16.13 The Lytic Cycle: A Strategy for Viral Reproduction
16.3 How Do Viruses Regulate Their Gene Expression?
2. Late stage: viral late genes are
transcribed (positive regulation).
They encode the viral capsid proteins
and enzymes to lyse the host cell.
The whole process from binding and
infection to release of new particles
takes about 30 minutes.
16.3 How Do Viruses Regulate Their Gene Expression?
Some viruses have evolved
lysogeny—the lytic cycle is delayed.
Viral DNA integrates with the host DNA
to form a prophage.
As the host cell divides, the viral DNA
replicates too and can last for
thousands of generations.
Figure 16.14 The Lytic and Lysogenic Cycles of Bacteriophages
16.3 How Do Viruses Regulate Their Gene Expression?
If a host cell is not growing well, the
virus may switch to the lytic cycle.
The prophage excises itself from the
host chromosome and reproduces.
Understanding the regulation of gene
expression that underlies the
lysis/lysogeny switch was a major
achievement.
16.3 How Do Viruses Regulate Their Gene Expression?
How does the prophage “know” when
to switch?
Two virus genes encode regulatory
proteins cI and Cro.
cI blocks expression of genes for the
lytic cycle and promotes expression of
genes for lysogeny; Cro has the
opposite effect.
16.3 How Do Viruses Regulate Their Gene Expression?
If conditions are favorable for host cell
growth, cI accumulates and
outcompetes Cro for DNA binding;
phage enters lysogenic cycle.
If host cell is under stress, cI is
degraded and no longer blocks
expression of Cro; phage enters lytic
cycle.
Figure 16.15 Control of Bacteriophage  Lysis and Lysogeny
16.3 How Do Viruses Regulate Their Gene Expression?
cI protein is degraded because it is
structurally similar to E. coli protein
LexA that is also degraded.
LexA represses DNA repair
mechanisms under normal conditions,
but is degraded by other proteins
when the cell is stressed.
16.3 How Do Viruses Regulate Their Gene Expression?
Eukaryote viruses:
DNA viruses: Double- or singlestranded (complementary strand is
made in the host cell)
Some have both lytic and lysogenic
life cycles.
Examples: Herpes viruses and
papillomaviruses (warts).
16.3 How Do Viruses Regulate Their Gene Expression?
RNA viruses: Usually single-stranded
RNA is translated by the host cell to
make viral proteins involved in RNA
replication.
Example: Influenza virus.
16.3 How Do Viruses Regulate Their Gene Expression?
Retroviruses: RNA virus with a gene
for reverse transcriptase—
synthesizes DNA from an RNA
template.
The DNA copy is inserted into the
host genome.
Example: Human immunodeficiency
virus (HIV).
16.3 How Do Viruses Regulate Their Gene Expression?
HIV regulation occurs at the elongation
stage of transcription.
HIV is an enveloped virus—enclosed
in a phospholipid membrane derived
from the host.
The envelope fuses with the host cell
membrane, the virus enters, and its
capsid is broken down.
Figure 16.16 The Reproductive Cycle of HIV
16.3 How Do Viruses Regulate Their Gene Expression?
Reverse transcriptase uses the viral
RNA to make a complementary DNA
(cDNA) strand.
A copy of the cDNA is also made, and
the double-stranded cDNA is inserted
into host chromosome by integrase.
The inserted DNA is called a
provirus.
16.3 How Do Viruses Regulate Their Gene Expression?
The provirus resides permanently in the
host chromosome, and can be
inactive (latent) for years.
Transcription of viral DNA is initiated,
but host cell proteins prevent
elongation.
Figure 16.17 Regulation of Transcription by HIV (Part 1)
16.3 How Do Viruses Regulate Their Gene Expression?
Under certain conditions, transcription
initiation increases, and some viral
RNA is made, including RNA for a
protein called tat (transactivator of
transcription).
tat binds to the viral RNA and
production of full-length viral RNA is
dramatically increased. The rest of the
viral life cycle then proceeds.
Figure 16.17 Regulation of Transcription by HIV (Part 2)
16.3 How Do Viruses Regulate Their Gene Expression?
Nearly every step in the HIV life cycle is
a potential target for anti-HIV drugs:
• Reverse transcriptase inhibitors (step
2)
• Integrase inhibitors (step 3)
• Protease inhibitors block
posttranslational processing of viral
proteins (step 5)
16.3 How Do Viruses Regulate Their Gene Expression?
Combinations of drugs have been very
successful at treating HIV infection,
but new strains rapidly emerge.
New drugs are being developed to
target other life cycle steps, including
drugs that interfere with binding of
virus to host cell, and interfere with tat
activity.
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Epigenetics is the study of changes in
gene expression that occur without
changes in the DNA sequence.
These changes are reversible, but
sometimes stable and heritable.
Includes two processes: DNA
methylation and chromosomal
protein alterations.
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Methylation:
• A methyl group is covalently added to
the 5′ carbon of cytosine, forming 5methylcytosine
• Catalyzed by DNA
methyltransferase
• Usually occurs in regions rich in C and
G doublets, called CpG islands—
often in promoters
16.4 How Do Epigenetic Changes Regulate Gene Expression?
It can be heritable: when DNA
replicates, a maintenance methylase
catalyzes formation of 5methylcytosine in the new strand.
Or, the methylation pattern may be
altered because it is reversible.
Demethylase catalyzes removal of
methyl groups.
Figure 16.18 DNA Methylation: An Epigenetic Change (Part 1)
Figure 16.18 DNA Methylation: An Epigenetic Change (Part 2)
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Effects of DNA methylation:
• Methyl groups in promoter regions
attract proteins for transcription
repression. Methylated genes are
often inactive
• In development, early demethylation
allows many genes to become active
Later, some genes may be “silenced”
by methylation
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Silent genes may be turned back on:
DNA methylation can play a role in
cancer—oncogenes get activated and
promote cell division, and tumor
suppressor genes can be turned off.
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Chromosomal protein alterations or
chromatin remodeling:
DNA is packaged with histone proteins
into nucleosomes. The DNA is
inaccessible to RNA polymerase and
transcription factors.
The histones have “tails” with positively
charged amino acids, which are
attracted to negatively charged DNA.
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Histone acetyltransferases add acetyl
groups to the tails which changes their
charges, and opens up the
nucleosome to activate transcription.
Figure 16.19 Epigenetic Remodeling of Chromatin for Transcription
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Histone deacetylases removes the
acetyl groups, which represses
transcription.
In some cancers, genes that inhibit cell
division are excessively deacetylated.
Drugs that inhibit histone deacetylase
may be useful to treat the cancer.
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Histones can also be modified by:
• Methylation—inactivates genes
• Phosphorylation—effects depend on
which amino acids are involved
All the epigenetic effects are reversible,
so gene activity may be determined
by very complex patterns of histone
modification.
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Environmental factors can induce
epigenetic changes:
Monozygotic (identical) twins have
identical genomes, and have been
used to study epigenetic effects.
In 3-year-old twins, DNA methylation
patterns are the same. By age 50,
when twins have been living apart in
different environments, methylation
patterns were quite different.
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Genomic imprinting:
In mammals, eggs and sperm develop
different methylation patterns.
For about 200 genes, offspring inherit
an inactive (methylated) copy and an
active (demethylated) one.
Figure 16.20 Genomic Imprinting
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Example of imprinting: a region on
human chromosome 15 called 15q11
Rarely, a chromosome deletion results
in the baby having only the male or
female version of the gene.
• Male pattern results in Angelman
syndrome, with epilepsy, tremors, and
constant smiling
16.4 How Do Epigenetic Changes Regulate Gene Expression?
• Female pattern results in Prader-Willi
syndrome, marked by muscle
weakness and obesity
The gene sequences are the same in
both cases; the epigenetic patterns
are different.
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Patterns of DNA methylation may
include large regions or whole
chromosomes.
Two kinds of chromatin:
• Euchromatin—diffuse, light-staining;
contains DNA that is transcribed
• Heterochromatin—condensed, darkstaining, contains genes not
transcribed
16.4 How Do Epigenetic Changes Regulate Gene Expression?
One type of heterochromatin is the
inactive X chromosome in mammals.
Males (XY) and females (XX) contain
different numbers of X-linked genes,
yet for most genes transcription rates
are similar.
Early in development, one of the X
chromosomes in females is
inactivated.
16.4 How Do Epigenetic Changes Regulate Gene Expression?
Which X chromosome gets inactivated
is random in each cell.
The inactivated X chromosome is
heterochromatin, and shows up as a
Barr body in human female cells.
The DNA is heavily methylated, and
unavailable for transcription, except
for the Xist gene.
Figure 16.21 X Chromosome Inactivation
16.4 How Do Epigenetic Changes Regulate Gene Expression?
RNA transcribed from Xist (X
inactivation-specific transcript) binds
to the chromosome, spreading the
inactivation.
This RNA is an example of
interference RNA.
Figure 16.21 X Chromosome Inactivation
16.5 How Is Eukaryotic Gene Expression Regulated After
Transcription?
After transcription, eukaryotic gene
expression can be regulated in the
nucleus before mRNA export, or after
mRNA leaves.
Control mechanisms include alternative
splicing of pre-mRNA, gene silencing,
translation repressors, and regulation
of protein breakdown.
16.5 How Is Eukaryotic Gene Expression Regulated After
Transcription?
Alternative splicing: different mRNAs
can be made from the same gene.
Introns are spliced out; mature mRNAs
have none.
Sometimes exons are spliced out too—
resulting in different proteins.
There are many more human mRNAs
than there are coding genes.
Figure 16.22 Alternative Splicing Results in Different Mature mRNAs and Proteins
16.5 How Is Eukaryotic Gene Expression Regulated After
Transcription?
MicroRNAs(miRNAs): small RNAs
produced by noncoding regions of
DNA.
First found in C. elegans. Two genes
effect transition through the larval
stages:
• Mutations in lin-14 caused the worm
to skip the 1st stage; normal role is to
facilitate stage 1 events.
16.5 How Is Eukaryotic Gene Expression Regulated After
Transcription?
• lin-4 mutations caused some cells to repeat
a development pattern normally shown in
the 1st stage; its normal role is negative
regulation of lin-14.
lin-14 encodes a transcription factor that
affects genes involved in larval cell
progression.
lin-4 encodes a 22-base miRNA that
inhibits lin-14 expression posttranscriptionally, by binding to its mRNA.
16.5 How Is Eukaryotic Gene Expression Regulated After
Transcription?
The human genome has about 1,000
miRNA encoding regions.
miRNAs can inhibit translation by
binding to target mRNAs. Each one is
about 22 bases long and has many
targets, as binding doesn’t have to be
perfect.
Figure 16.23 mRNA Inhibition by RNAs (Part 1)
16.5 How Is Eukaryotic Gene Expression Regulated After
Transcription?
Small interfering RNAs (siRNAs) also
result in RNA silencing.
Often arise from viral infection and
transposon sequences. They bind to
target mRNA and cause its
degradation.
May have evolved as defense to
prevent translation of viral and
transposon sequences.
Figure 16.23 mRNA Inhibition by RNAs (Part 2)
16.5 How Is Eukaryotic Gene Expression Regulated After
Transcription?
Cells have two major ways to control
the amount of protein after
transcription:
• Block mRNA translation
• Alter how long new proteins persist in
the cell
16.5 How Is Eukaryotic Gene Expression Regulated After
Transcription?
Translation can be altered by:
• miRNAs that inhibit translation
• GTP cap on 5′ end of mRNA can be
modified—if cap is unmodified mRNA
is not translated
• Repressor proteins can block
translation directly
16.5 How Is Eukaryotic Gene Expression Regulated After
Transcription?
Translational repressor proteins can
bind to noncoding regions of mRNA
and block translation by preventing it
from binding to a ribosome.
The RNA region that is bound by the
repressor is called a riboswitch.
Figure 16.24 Translational Repressor Can Repress Translation
16.5 How Is Eukaryotic Gene Expression Regulated After
Transcription?
Protein longevity:
Protein content of a cell is a function of
synthesis and degradation.
Proteins can be targeted for destruction
when ubiquitin attaches to it and
attracts other ubiquitins, forming a
polyubiquitin chain.
16.5 How Is Eukaryotic Gene Expression Regulated After
Transcription?
The complex binds to a proteasome—
a large complex where the ubiquitin is
removed and the protein is digested
by proteases.
Figure 16.25 A Proteasome Breaks Down Proteins
16.5 How Is Eukaryotic Gene Expression Regulated After
Transcription?
Some strains of human papillomavirus
(HPV) add ubiquitin to p53 and
retinoblastoma proteins, targeting
them for degradation.
These proteins normally inhibit the cell
cycle, so the result of this HPV activity
is unregulated cell division (cancer).
16 Answer to Opening Question
Epigenetic changes often involve
methylation.
Some nutrients, such as folic acid,
have methyl groups and participate in
DNA modification.
Experiments with mice show that diets
rich in these nutrients change
epigenetic patterns that remain
throughout life.