Download Translational Control

From Gene to Protein
The Central Dogma
GENES determine traits by building individual proteins for that trait
An
error in the gene = an error in the protein
The Central
Dogma
DNA
RNA
Amino Acid Chain
(Protein)
Figure 14.3
DNA holds the instructions,
while RNA carries out the
instructions. RNA is a lot
like DNA, except:
1. Ribose
2. Uracil
3. Single Strand
4. RNA can leave the
nucleus, thus carries the
"message"
Figure 14.5
The instructions on
mRNA (messenger
RNA) are read by the
ribosome as a series
of 3 bases called a
CODON
Each CODON
specifies one AMINO
ACID.
Some amino acids are
repeated (third base
wobble) to minimize
mutations
Figure 14.6
TRANSCRIPTION:
The process where mRNA is
made from DNA
Follows base-pair rule
has uracil instead of thymine
RNA polymerase is used to
build the strand of mRNA
Where have you heard the
term “polymerase” before?
Transcription Animations
Transcription: Stolaf.edu
Transcription: University of Nebraska
Transcription: Concord.org
Translation: process by which protein
is built from the mRNA
Occurs at the
ribosome (rRNA)
tRNA brings amino
acids to the
developing protein
chain
Each 3 bases on
mRNA (called a
codon) codes for a
single amino acid
by matching the
anti-codon on tRNA
3 bases on mRNA
= a codon
Matching 3 bases on
tRNA
= anticodon
Before translation
begins, a tRNA must
be “charged.” This
ACTIVE process
occurs when an
enzyme attaches the
appropriate amino
acid.
Transcription (AP Level)
-
-
-
-
Transcription begins at the start of the gene called the
promoter region. Enzymes bind to a “start” area called the
TATA box. Each gene has its own promoter, so they cell
can choose which genes to transcribe when.
After the enzymes are bound, the enhancer region
(upstream from the start) trigger the enzymes to begin
transcription. (This requires ATP.)
RNA polymerase unzips and copies the needed gene onto
an mRNA strand until the termination sequence (end of
gene) is reached.
The mRNA strand is then released, and the DNA rezips.
After Transcription
- The mRNA must be edited
before it can leave the
nucleus and be used.
- Introns (junk DNA) are
removed, exons (needed
DNA) are spliced back
together by proteins called
SNRPs. As a group, the
SNRPs are called the
Spliceosome.
- A cap and a tail are added to
protect the mRNA. Longer
tails mean the mRNA can be
used more often.
Alternative Splicing
- Note: the same mRNA can be edited different ways.
This alternative splicing allows the cell to modify the
eventual protein being made and make different
proteins from the same original mRNA template.
After Transcription comes…
TRANSLATION
Translation occurs on the ribosome in a series of steps.
1- initiation: the small subunit of the ribosome bonds to the
start codon (AUG) of the mRNA. The appropriate charged
tRNA (anti-codon UAC) links to the start codon. The large
subunit of the ribosome attaches and the process begins. (If
AUG is always the start codon, what is always the starting
amino acid?)
Translation occurs on the ribosome in a series of steps.
2- elongation: the ribosome complex then moves along the
mRNA reading each codon. New, appropriately charged tRNA
molecules enter at the A site of the ribosome, release their
amino acid to the growing polypeptide chain at the P site, and
leave (un-charged without their amino acid) at the E site. Note:
The un-charged tRNA can be recharged and reused
Translation occurs on the ribosome in a series of steps.
3- termination: When the ribosome reaches a stop codon, the
entire complex releases and the created polypeptide chain
begins protein folding. Note: Several ribosomes can translate
the same piece of mRNA simultaneously to boost protein
production.
amino acids
A U G
TRANSLATION (protein synthesis)
* All genes start with AUG, also called the START CODON
It attaches to anticodon UAC and the amino acid methionine.
This is the big
picture. Can
you explain it
in your own
words?
Animations of Translation
Translation: Stolaf.edu
Translation: University of Nebraska
Translation: Concord.org
Regulation of Gene
Expression
Consider that....
Every cell of the body contains ALL the DNA for the organism.
Not all genes are necessary all the time
Cells must have the ability to turn a gene on and off
ENTER: THE OPERON MODEL
OF GENE EXPRESSION
Operons and Gene Control
Experiments with E. Coli showed that it is capable of
regulating the expression of its genes as gene sets called
“operons”.
A prokaryote operon consists of the following elements
1. Promoter - gene sequence where RNA polymerase
attaches, signalling the start of the gene group
2. Operator - where a repressor
binds, stopping the transcription of
that gene
3. Structural Genes - genes
coding for needed proteins, they
are transcribed as a unit
The trp Operon
It controls the production of tryptophan, a necessary amino
acid.
If tryptophan is already present, it binds to and activates the
repressor to prevent more tryptophan from being made
The lac Operon (which produces lactase enzymes and helper
proteins). In this case, the prokaryote only needs lactase when
lactose is present. This gene is essentially the reverse of trp in
that the presence of lactose deactivates the repressor and
turns on the gene.
REMEMBER!
Operons are only found in prokaryotes, but gene control in
eukaryotes is similar. A little more complicated, but similar.
Repressors versus Inducers
The trp operon is a repressible operon, it is normally on but
can be turned off when tryptophan is present. A repressor
turns off a gene.
The lac operon is an inducible operon because it is normally
off but can be turned on when lactose is present. An inducer
turns on a gene.
Grammar Time
A woman is pregnant and the baby is
later. The doctor says they will "INDUCE"
labor tomorrow. What does he mean?
In eukaryotes, a
variety of
mechanisms regulate
gene expression
1. chromatin structure
2. transcriptional control
3. post transcriptional control
4. translational control
5. post translational control
Chromatin Structure
Eukaryote DNA is wound
around protein molecules
called histones. More
tightly wound regions
cannot be reached for
transcription. Less tightly
wound are more easily
accessed.
The others are pretty
self-explanatory once
you practice your
vocabulary!
Chromatin Structure ExampleBARR BODIES
In females, chromatin of one of the X chromosomes winds so
tightly that it inactivates, this inactive chromosome is called a
BARR BODY. This method of control can also be used in codominant pairs.
Barr Body in Cats
Genotype:
XB XO
The black patches are XB and the
orange patches are XO, the cat is
multicolored because not all X's are
activated
Eukaryotic Gene Control
-
Transcriptional Control (stop/start transcription)
Post-transcriptional Control (modify the mRNA)
Translational Control (stop/start translation)
Post-translational control (modify the protein)
-
Remember that the cell is in control every step of the way.
At any point, the cell can stop the process or modify the
results of the process.
Gene Mutations
Point Mutations - single base changes, causing a
change in the amino acid structure (protein); usually
only one amino acid is changed.
Frameshift mutation
1-2 bases are added or deleted, shifting all codons
downstream. This changes MULTIPLE amino acids in the
protein.
GAT
CAT
AAA
GAT
A CA TAA A
Effect of Mutation on Protein
-
-
-
-
If the change results in replacement by the same amino
acid (thanks to the third base wobble) and therefore a
normal protein, this is called a “silent mutation” bc nothing
actually changes.
If the change results in one single amino acid change, this
is called a “missense mutation” bc the protein may still
work, but not as before.
If the change results in multiple amino acid changes or a
stop codon in the middle, this is called a “nonsense
mutation”. Typically these proteins do not function at all.
Note: if a mutation can make a protein WORSE, it can also
make it BETTER. The occasion of improved proteins are
critical for evolutionary change.
What happens when you have a
nonfunctional protein?
Hemophilia
PKU
Cystic Fibrosis
Etc.
Mutations and Cancer
If a TUMOR SUPPRESSOR GENE (Protein p53) is mutated,
this often results in increased cancer risk.
When ONCOGENES (cancerous genes) activate, cell division
occurs uncontrollably and tumors form
Example: Breast Cancer Gene
BRCA1 (pronounced brak-uh 1)