Transcript Control of Gene Expression

Control of Gene
Expression
The Central Dogma
From DNA to Proteins
Genotype
DNA
Transcription
RNA
Translation
Protein
Phenotype
Review of Replication, Transcription
and Translation
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DNA Replication
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Ch9 Q3
Note primase and Okazaki fragments
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Transcription + Translation

Protein Synthesis
Control of Gene Expression

Every somatic cell has the same DNA

Cells are very different because each cell
makes certain proteins and not others

How does a cell know which genes to
transcribe and which not to?
Transcription Factors

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Proteins which control the expression of other
genes
Link the genome with the environment
Activated by signals from outside the cell (e.g.
hormones, sugar, etc.)
Allow RNA polymerase to bind to the
promoter so that transcription can begin
Gene must also be exposed –DNA must
unwind in that area.
RNA Processing

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The average total size of a gene is 27,000
bases but the average size of the coding
portion is only 1,340 bases!
mRNA transcripts are modified before use
as a template for translation:

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Addition of capping nucleotide at the 5’ end
Addition of polyA tail to 3’ end
Important for moving transcript out of nucleus
and for regulating when translation occurs
RNA Processing -Splicing

Splicing occurs, removing internal sequences

Introns are sequences removed

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Exons are sequences remaining
There is alternate splicing of mRNA in different
tissues

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Introns =Intervening sequences
Used to be called Junk DNA!
The # of proteins (~200,000) far outnumbers the # of genes
(~20,000)
An intron in one context may be an exon in another
context
RNA Processing
Figure 10.10
Translation:
Multiple Copies of a Protein Are
Made Simultaneously
Figure 10.16
Protein Conformation

Primary (1) structure

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Secondary (2) structure

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Folding of the protein into -helices and -pleated sheets
Tertiary (3) structure

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Sequence of amino acids
3D shape
Quaternary (4) structure

Complex with other polypeptides (same or different
proteins)
The Proteasome

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Misfolded proteins have ubiquitin molecules attached
to them
Ubiquitinated proteins are sent to the proteasome to
be degraded
Prions

Sole difference between normal and disease
protein is conformation
Normal PrPC
conformation
with many helices

Infectious
PrPSc
conformation
with -sheets
All mammals have PrP but nearby proteins and
polysaccharides keep it correctly folded
Spread of Prion Disease
PrPC
PrPSc
Spongiform Encephalopathies
Gene Expression Can Change Over
Time

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Example: Globin chain
switching
Hemoglobin molecules

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Transport oxygen
molecules in the blood
Composed of 4 globular
proteins
Globin Chain Switching
Figure 11.2
Proteomics

Looking at all of the proteins made in a particular
cell (or tissue, organ, etc.)

i.e. the proteome
Chromatin Remodeling

DNA is wrapped around histones to form
nucleosomes

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Acetylation =acetyl groups are added to
histones

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Chromosome packaging
Exposes the primer so RNA polymerase can bind
and transcription can begin
Deacetylation =acetyl groups are removed
from histones
RNA Interference
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Occasionally, both DNA strands are
transcribed
Complementary strands bind to one another
Gene sequence may allow formation of a
“hairpin loop”
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RNA strand binds to itself
Segments of dsRNA attract RNA-induced
silencing complexes (RISCs)
Can be used experimentally (clinically?)
RNA Interference