Control of Gene Expression 2: Post transcriptional control Flashcards
RNA splicing can be regulated negatively by what? and what does it do?
repressor molecule that prevents splicing machinery access to splice sites
How can RNA splicing be regulated positively? and how?
by activating molecule that recruits and helps direct splicing machinery
What do mRNAs have to confer stability?
poly A tail
What are the steps in regulation by RNA stability?
- decapping: exposed mRNA degraded from 5’ end
2. mRNA degraded from 3’ end through poly-A tail and into coding region
What does ferritin mRNA do?
storage of iron
what does TfR mRNA do?
iron absorbance
Describe ferritin
intracellular protein
binds thousands of Fe 3+/molecule
found in most cells
What is hemosiderin?
granules of ferritin
Where is excess of iron stored?
liver
lungs
pancreas
What happens during iron starvation?
decrease ferritin mRNA (encodes storage of protein)
cells must transport iron into cells
make more transferrin receptor (TfR) mRNA
What happens during iron in excess?
make more ferritin mRNA
transport less iron out of the cell
make less TfR mRNA
What are iron responsive elements (IREs)
recognition sites for binding
What are iron responsive regulatory protein (IRP)
aconitase
What happens when IRP binds to IRE at 5’ ferritin mRNA
no ferritin- translation is blocked
What happens when IRP binds to IRE at 3’ transferrin receptor mRNA
transferrin receptor made-mRNA stable
What happens if IRP does not bind to IRE at 5’ ferritin mRNA
mRNA made- get ferritin
What happens if IRP does not bind to IRE at 3’ transferrin receptor mRNA
RNA degrades and no transferrin receptor made
What are noncoding RNAs?
22 nucleotides long that silence expression of specific mRNA targets
What are microRNAs?
regulatory RNAs that regulate messenger RNAs
Are the changes in microRNA expression causative of disease or responsive to disease?
yes
Causative
miRNAS likely to have mutations that cause the disease
Responsive
increased miRNA expression down regulates genes in response to disease to limit severity
What is found in the involvement of Tourettes syndrome?
1 form of miRNA, SLITRK1 variant
What happens if there is a change in recognition sequence on target SLITRK1 mRNA?
increased miRNA binding
What is required by proteins to be functional?
post translational modification
What are proteins modified by?
protein kinase
What is synthesized in dramatic amounts when the temperature is raised?
heat shock proteins (Hsp)
Why are Hsp made dramatically when temp is raised?
increase in temperature leads to increase in misfolding proteins and the Hsp help with refolding
What does the proteasome do?
removes misfolded proteins, deliberately destroys aberrant proteins
How do you recognize a protein for destruction?
ubiquitin removes unfolded or abnormal proteins
How does ubiquitin remove abnormal proteins?
with a recognition tag that marks them for destruction
Proteasome inhibitors can be used to treat _________
multiple myelomas
What is a myeloma?
cancer of plasma cells
What is Bortezomib?
inhibitor of proteasome
How does bortezomib world?
interacts with 1 proteolytic site-reversibly inhibits proteasome
What are four controls of gene expression?
- coordinated expression of genes: genes don’t exist in a vacuum
- decision for specialization: what kind of cell do I want to be?
- Methylation and genomic imprinting: what genes get expressed (or not) from mom and dad
- X chromosome inactivation: even things out XX vs XY
What is genomic imprinting?
differential expression of genetic material depending on the parent of origin
What is epigenetic?
regulation of expression of gene activity without altering gene structure
What causes Prader Willi (PWS) syndrome?
paternal deletion of chromosome 15 in the region 15q11-q13
What are the stages of PWS?
stage one: infantile hypotonia; poor suck; feeding difficulties- failure to thrive
stage two: hyperphagia (uncontrollable eating), onset of early childhood obesity
What is x inactivation?
In females, one of the X chromosomes becomes very condensed and turns into a Barr body, this chromosome is not expressed
True or false? MicroRNAS bind to mRNAs to activate the mRNAs to produce large amounts of protein
False
