Control of Gene Expression Flashcards
What does failure to regulate gene expression lead to?
Metabolic disease
Metastasis
Congenital disorders
Cancer
What is beta-thalassaemia?
A group of genetic diseases caused by insufficient expression of beta-globin
In most types of beta-thalassaemia, the beta-globin protein is structurally normal
Multiple independently arising forms of the disease
Mutations causing beta-thalassaemia map to multiple sites in the beta-globin gene
For example:
1.Mutation can occur in the TATA box so, therefore, the transcription cannot start leading to the underproduction of beta-globin due to under-expression
2.Mutation in the intron where the intron is no longer spliced therefore remains in the sequence and is degraded in the nucleus as it’s incorrect
What is an instance of translational control?
Early embryogenesis- during the first 4-8 cell divisions there is virtually no gene expression
At the end of the blastocyst formation first genes to be expressed are due to up-regulation of translation from maternally-derived pre-formed mRNAs
Environmental stress- exposure to heat shock or pathogens can cause global changes in translation
Many specific examples e.g. ferritin
What is always the first codon?
Always the first AUG AFTER the Kozak sequence
What involvement does the UTR have in the control of gene expression
The 5’ UTR is not the bit that determines whether a ribosome binds, but it does play a major role in determining how efficiently the ribosome initiates translation
e.g.
Globin (very efficiently translated)
Ferritin (very inefficiently translated)
3’UTR can play a role in determining the stability of the mRNA
3’UTRs confer very different stabilities on mRNAs:
GLobin 3’UTRs confer stability
Immune stress hormones (very unstable mRNAs)
How are intracellular iron levels translationally controlled?
Ferritin- binds iron and retains in the cytoplasm as a store for excess
Only ferritin at times of excess
Ferritin is a protein that acts as a sponge for ions
The Fe starvation inhibitor blocks ferritin from being translated
When there is plenty of iron the iron binds to the inhibitor leading to a conformational change releasing the hairpin structure so ferritin is able to be expressed
What are miRNAs and what are their functions?
The human genome encodes over 500 small non-coding RNAs that are transcribed by RNA polymerase II
These RNAs are referred to collectively as microRNAs or miRNAs
These miRNAs act to control the post-translational regulation of as many as one third of all human genes
Any given miRNA can regulate several target genes
How are miRNAs formed?
MicroRNAs are derived by processing from a larger precursor
This processing involves the removal of the single-stranded RNA parts of the molecule
This small double-stranded miRNA is recognised by proteins in the cytoplasm called RISC proteins (RNA-induced silencing complex
The RISC protein binds to the double-stranded RNA molecule and separated the molecule into a single strand of RNA
What is the mechanism of action of miRNAs?
Now the RISC protein complex will go and find complementary targets for this RNA molecule
You can have an extensive match with another pre-existing RNA molecule
Then the RISC protein would degrade the double stranded RNA (a clean way of degrading RNA)
Some of it can target an mRNA bind part of itself to mRNA which would then mean that the ribosome will not be able to move along the mRNA
And the mRNA will be degraded
These are processes to regulate gene expression
