Transcript Gene Regulation

Gene Regulation
• In 1961, Francois Jacob and Jacques
Monod proposed the operon model for the
control of gene expression in bacteria.
• An operon consists of three elements:
– the genes that it controls,
• In bacteria, the genes coding for a protein are
transcribed (or not) as one long mRNA molecule.
– a promoter region where RNA polymerase first
binds,
– an operator region between the promoter and
the first gene which acts as an “on-off switch”.
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• By itself, an operon is always avaliable for
transcription and RNA polymerase can bind
to the promoter and transcribe the genes.
Fig. 18.20a
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• However, if a repressor protein, a product of
a regulatory gene, binds to the operator, it
can prevent transcription of the operon’s
genes.
– Each repressor protein recognizes and binds
only to the operator of a certain operon.
– Regulatory genes are transcribed at low rates
continuously.
Fig. 18.20b
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• The lac operon, containing a series of genes that
code for enzymes, which play a major role is the
hydrolysis and metabolism for lactose.
• In the absence of lactose, this operon is off
as an active repressor binds to the operator
and prevents transcription.
Fig. 18.21a
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•
When lactose is present in the cell, allolactase, an
isomer of lactose, binds to the repressor.
This inactivates the repressor, and the lac operon
can be transcribed (is turned on).
•
Fig. 18.21b
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•Both repressible and inducible operons
demonstrate negative control because active
repressors can only have negative effects on
transcription.
•Positive gene control occurs when an activator
molecule interacts directly with the genome to
switch transcription on or enhance transcription.
Eukaryotic cells modify RNA after
transcription
• Enzymes in the eukaryotic nucleus modify
mRNA before the genetic messages are
dispatched to the cytoplasm.
• Following transcription, at the 5’ end of the
mRNA molecule, a modified form of guanine
is added, the 5’ cap and a poly-A tail.
– These helps protect mRNA from hydrolytic
enzymes.
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• Eukaryotic genes contain parts of the
nucleotide sequence that is transcribed
and then removed before translation.
• Exons are spliced together to form the
final mRNA that is translated.
• Introns are the sequences removed
before translation
RNA Processing
Fig. 17.9
• RNA splicing removes introns and joins exons to
create an mRNA molecule with a continuous
coding sequence.
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• RNA splicing appears to have several
functions.
– First, at least some introns contain sequences
that control gene activity in some way.
– Splicing itself may regulate the passage of
mRNA from the nucleus to the cytoplasm.
– One clear benefit of split genes is to enable a
one gene to encode for more than one
polypeptide.
• Alternative RNA splicing gives rise to two
or more different polypeptides, depending
on which segments are treated as exons.
– Results of the Human Genome Project indicate
that this phenomenon is common in humans.
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• Split genes may also facilitate the evolution
of new proteins.
• Proteins often have a
modular architecture
with discrete structural
and functional regions
called domains.
• In many cases,
different exons
code for different
domains of a
protein.
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Fig. 17.11
Point mutations can affect
protein structure and function
• Mutations are changes in the genetic material of a
cell (or virus).
• These include large-scale mutations in which long
segments of DNA are affected (for example,
translocations, duplications, and inversions).
• A chemical change in just one base pair of a gene
causes a point mutation.
• If these occur in gametes or cells producing
gametes, they may be transmitted to future
generations.
• Substitution: For example, sickle-cell disease
is caused by a mutation of a single base pair
in the gene that codes for one of the
polypeptides of hemoglobin.
– A change in a T to A (substitution) in the DNA
template leads to an abnormal protein.
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Fig. 17.23
Missense Mutation
Nonsense Mutation
Frameshift Mutations:
Insertion and Deletion Point Mutations
• Insertion: A single nucleotide base is inserted
into a DNA sequence.
• Deletion: A single nucleotide is removed to a
DNA sequence.
• How the ribosome reads the nucleotide
codons changes ie. it changes the reading
frame.
Deletion
Insertion
Fig. 17.24
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