Flashcards in Control Of Gene Expression II Deck (58):
How can RNA splicing be negatively regulated?
By repressor moleculs that prevents splicing machinery access to splicing sites.
How can RNA splicing be regulated positively?
By activating molecules that recruit and help direct splicing machinery.
How do mRNAs leave the nucleus?
How do mRNAs travel to their destinations?
By using cytoskeletal motors. Anchor proteins hold mRNA in place.
What happens to RNA that is not trapped?
It is degraded
What is found on the end of mRNA that contributes to its stability?
A poly-A tail.
It acts as a timer; once reduced to 25 nucleotides, two pathways converge to degrade mRNA.
Where is exposed mRNA degraded from?
The 5' end. The 5' cap serves to protect RNA from RNA degrading enzymes.
Regulation by RNA stability:
2. MRNA degraded from 3' end through poly-A tail and into coding region.
What is the control of RNA involved in?
Iron transport from the intestine to bone marrow involves the discovery of what?
Many proteins that have been recently discovered.
What is the pathway of the iron cycle?
Gut lumen -> intestinal absorption -> plasma transferrin ion -> TfR (marrow erythroid precursors) -> circulating erythrocytes -> macrophages -> back to plasma transferrin ion, which is also found in the liver.
What is the function of ferritin?
It binds thousands of Fe3+ molecules and is found in most cells.
What is hemosiderin?
Granules of the ferritin protein.
In what organs is excess iron mainly stored by?
What occurs during iron starvation?
A decrease in ferritin mRNA.
Cells must transport iron into cells, and transferrin receptor is made in order to do so.
What occurs during excess iron?
Excess iron needs to be stored.
More ferritin mRNA is made, and less is transported into the cell.
Less TfR mRNA is made (makes Fe transport protein).
What does mRNA regulation involve?
Iron responsive elements (IREs) and iron responsive regulatory protein (IRP) aconitase.
Where does IRP bind to IRE?
At 5' ferritin mRNA (this causes no ferritin to be produced)
At 3' transferrin receptor mRNA (transferrin receptor is made).
What are microRNAs?
Regulatory RNAs that regulate messenger RNAs.
These are noncoding RNAs that silence the expression of specific mRNA targets.
Where to miRNAs bind?
To complementary sequences in the 3' UT nd of mRNA.
What is the function of miRNAs?
They degrade RNA or block translation.
How do microRNAs affect gene activity?
They repress gene activity.
What are the components of the RNA-induced silencing complex (RISC)?
MicroRNA, argonaute and other proteins.
What does miRNA base pair with?
What does microRNA cleave?
It also shuts down its expression.
Each miRNA can repress ___ of mRNAs.
MiRNA binding sites are widespread, and 1 miRNA can affect a whole biological program.
What happens to miRNA during disease states?
MiRNAs change their expression profile.
For example, certain miRNAs can be elevated in stroke or cardiovascular disease.
Are the changes in microRNA expression causative of disease or responsive to disease?
Causative: miRNAs likely hav mutations that cause diseases.
Responsive: increased miRNA expression down regulates genes in response to disease to limit severity.
What is a disease that is indicivative of the causative nature of miRNAs?
MiRNA involvement was found with 1 form of Tourette's Syndrome.
A change in the recognition sequence on target SLITRK1 mRNA -> increased miRNA binding.
How does miRNA cause Tourette's Syndrome?
MiR-189 binds more efficiently to target sequence in 3' UT of SLITRK1 gene and decreases SLITRK1 expression. This leads to Tourette's syndrome.
What helps proteins to fold into their 3D conformations and hence become functional?
What are some requirements of protein folding?
Folding and cofactor binding
Covalent modifications by glycosylation, phosphorylation, etc.
Binding to other protein subunits
Mature functional protein.
Many molecular proteins are heat shock protein, which are synthesized in dramatic amounts when temperature is raised. Why is this so?
An increase in temperature leads to an increase in the misfolding of proteins.
There is feedback to synthesize chaperons to help proteins fold. They are Hsp60 and Hsp70.
What is important for the regulation of proteins by degradation?
What is the function of the proteasome?
It controls protein activity by choosing what proteins are around.
It removes misfolded proteins.
The proteasome is an apparatus that destroys aberrant proteins.
What is the function of ubiquitin?
It removes unfolded or abnormal proteins.
It does so by linking cysteine side chains to E1 - E3 enzymes, and primes proteins for destruction.
What is the side chain on a protein that ubiquitin binds to?
A lysine side chain.
What is the specificity of a proteasome?
It is specific for two E1 ubiquitin activating enzymes and 1 proteasome but 30-40 ubiquitin conjugating enzymes and hundreds of E3 accessory proteins.
What are proteasome inhibitors used to treat?
Multiple myelomas (cancer of plasma cells)
The chamber in a proteasome has 3 proteolytic sites. Bortezomid interacts with 1 protelolytic site. What does it specifically inhibit?
How is ubiquitin ligase activated?
1. Phosphorylation by protein kinase.
2. Allosteric transition caused by ligand binding.
3. Allosteric transition caused by protein subunit addition.
What are the steps in the activation of a degradation signal?
1. Phosphorylation by protein kinase
2. Unmasking by protein dissociation.
3. Creation of destabilizing N-terminus.
What are other controls of gene expression?
1. Coordinated expression of genes: genes do not exist in a vacuum.
2. Decision for specialization
3. Methylation and genomic imprinting: what genes get expressed from mom and dad.
4. X chromosome inactivation: even things out XX vs. XY - 2 X chromosomes vs. 1 X chromosome.
What can the expression of critical regualtory proteins cause?
They can trigger a battery of downstream genes.
Coordinated gene expression is done in response to need.
For example: glucocorticoid cortisol - response to stress - increase blood sugar - aid in fat, protein, carbohydrate metabolism, diurnal.
What is the consequence of gene control?
It can produce many types of cells.
What are two major fates of blood cells?
HSC (hematopoietic stem cell)
HPC (hematopoietic pluripotent stem cell)
What can DNA be regulated by?
DNA itself can also be covalently modified.
Where does methylation of cytosine occur?
At CG sequences.
True or false: methylation is inherited, and DNA methylation of a parent strand serves as a template for a daughter strand.
What is genomic imprinting?
Differential expression of genetic material depending on the parent of origin.
What is epigenetics?
Regulation of expression of gene activity without altering gene structure (e.g. Methylation).
What is genomic imprinting based on?
What are examples of genomic imprinting disorders?
Prader Willi syndrome.
It is caused by paternal deletion on chromosome 15.
In genomic imprinting disorders, what is the significance of paternal gene expression?
Genes in the chromosomal region are not expressed when inherited from Mom, but are expressed when inherited from Dad.
What is the purpose of dosage compensation?
To inactivate an X chromosome in femals so that an equal number of genes expressed form the X chromosome are present in males and females.
In development, one X chromosome is inactivated in femals. When is it activated?
During gamete cell formation.
What is the X-inactivation center?
A region where inactivation of an X chromosome starts and spreads.