Control of Gene Expression 2: Post-Transcriptional Control Flashcards
Alternative splicing produces different forms of proteins from the same gene. What percentage of genes in humans undergo this process?
75
How is RNA splicing negatively regulated?
represor molecule that prevents splicing machinery access to splice site
How is RNA splicing positively regulated?
activating molecule that recruits and helps direct splicing machinery
What are the three types of spatial localization of mRNA?
- mRNAs travel to destination using cytoskeleton motors
- random movement
- random movement + degradation
In regards to regulation by RNA stability, the poly-A tail confers stability. The gradual shortening of the poly-A tail acts as a timer. Once reduced to 25 nucleotides, two pathways converge to do what?
degrade mRNA
In regards to regulation by RNA stability, if the mRNA is decapped, what happens?
degraded from 5’ to 3’
What is the following pathway?
Gut lumen -> intestinal absorbtion -> plasma transferin iron -> liver or marrow erythroid precursors -> circulating erythrocytes -> macrophages
the iron cycle
What is Ferritin?
intracellular protein that binds thousands of Fe3+ molecules
note: hemosiderin is granules of ferritin
Where is excess liver mainly stored?
liver, lungs, pancreas
What occurs during iron starvation?
cells do not need to store iron; decrease in ferritin mRNA; iron must be transported into cells; more tranferrin receptor mRNA must be made
What occurs when iron is in excess?
iron needs to be stored; transport of iron into cells decreases; more ferritin mRNA and less transferrin receptor mRNA
mRNA regulation by repression of translation and RNA degradation involves iron responsive elements (IREs) and iron responsive regulatory proteins (IRPs). What two spots does IRP bind and what is the result?
IRP binds to 5’ ferritin mRNA: no ferritin
IRP binds to 3’ transferrin receptor mRNA: transferrin receptor is made
What are miRNAs?
small, non coding RNAs that regulate mRNA by silencing expression of specific mRNA targets; degrade RNA or block translation
Where do miRNAs bind?
complementary sequences in the 3’ UT end of mRNA
What mechanism do miRNAs use?
after being cropped in nucleus, form double stranded loop structure that is cleaved by Dicer enzyme, join other proteins to form RNA induced silencing complex and base pairs with mRNA and cleaves RNA shutting down expression
True or false?
miRNAs change their expression profile in disease states
true
ex: miR-29 is decreased in heart disease, miR141 is elevated in prostate cancer
Explain how changes in miRNA expression are causative of disease and responsive to disease
causative: miRNAs likely have mutations that cause disease (Tourette’s syndrome)
responsive: increased miRNA expression down regulates genes in response to disease to limit severity
Molecular chaperonnes, protein kinases, glycosylation, partner proteins are all involved in what?
protein modification
Why are most molecular chaperones heat shock proteins?
increase in temperature leads to increase in misfiling of proteins. If chaperones are going to efficiently assist in protein folding, they need to be able to withstand heat
In regards to regulation by protein degradation, how does ubiquitin work?
removes unfolded or abnormal proteins; first identifies recognition tag and uses E1 ubiquitin activating enzyme. Ubiquitin links to cysteine side chain. Then ubiquitin is transferred to E2 ligase/E3 complex which is primed to destroy proteins
Another way ubiquitin works is by the addition of a protein with a degradation signal to ubiquitin ligase. What happens after this?
ubiquitin chain is added to lysine side chain on protein and the chain is recognized by proteasome
In regards to specificity of the ubiquitin complex, how many different E1, E2 and E3 proteins are there?
E1: 1
E2: 30
E3: hundreds
Glucocorticoid cortisol expression in response to stress - increase blood sugar - aid in fat -, protein, cab metabolism - diurnal etc. is a example of what?
coordinated gene expression
In regards to specialization of blood cells, heamtopoietic pluripotent stem cells have two options. What are they?
myeloid lineage or lymphoid lineage, meaning they can make a RBC, megakaryocyte, macrophage, or T or B cells
True or false?
methylation is inherited
true; genomic imprinting is based on DNA methylation
Define genomic imprinting
differential expression of genetic material depending on the parent of origin
Regulation of expression of gene activity without altering gene structure is called what?
epigenetics
Prader Willi syndrome is a genomic imprinting disorder. What causes it? What is its presentation?
parental deletion on chromosome 15 inherited from father; Stage one presentation: poor sucking. Stage two: early childhood obesity
What is paternal gene expression?
genes in a certain chromosomal region are not expressed when inherited from mom but expressed when inherited from dad
note: in PWS, paternal genes not expressed (deleted) and maternal genes not expressed even though they are present
Why does dosage compensation occur?
so number of genes expressed from X chromosome is equal in males and females
True or false?
In females, one of the X chromosomes is inactive.
true; called a barr body
