Control of Gene Expression 2: Post-Transcriptional Control

Question 1

Alternative splicing produces different forms of proteins from the same gene. What percentage of genes in humans undergo this process?

Answer 1

75

Question 2

How is RNA splicing negatively regulated?

Answer 2

represor molecule that prevents splicing machinery access to splice site

Question 3

How is RNA splicing positively regulated?

Answer 3

activating molecule that recruits and helps direct splicing machinery

Question 4

What are the three types of spatial localization of mRNA?

Answer 4

1. mRNAs travel to destination using cytoskeleton motors
2. random movement
3. random movement + degradation

Question 5

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?

Answer 5

degrade mRNA

Question 6

In regards to regulation by RNA stability, if the mRNA is decapped, what happens?

Answer 6

degraded from 5’ to 3’

Question 7

What is the following pathway?
Gut lumen -> intestinal absorbtion -> plasma transferin iron -> liver or marrow erythroid precursors -> circulating erythrocytes -> macrophages

Answer 7

the iron cycle

Question 8

What is Ferritin?

Answer 8

intracellular protein that binds thousands of Fe3+ molecules

note: hemosiderin is granules of ferritin

Question 9

Where is excess liver mainly stored?

Answer 9

liver, lungs, pancreas

Question 10

What occurs during iron starvation?

Answer 10

cells do not need to store iron; decrease in ferritin mRNA; iron must be transported into cells; more tranferrin receptor mRNA must be made

Question 11

What occurs when iron is in excess?

Answer 11

iron needs to be stored; transport of iron into cells decreases; more ferritin mRNA and less transferrin receptor mRNA

Question 12

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?

Answer 12

IRP binds to 5’ ferritin mRNA: no ferritin

IRP binds to 3’ transferrin receptor mRNA: transferrin receptor is made

Question 13

What are miRNAs?

Answer 13

small, non coding RNAs that regulate mRNA by silencing expression of specific mRNA targets; degrade RNA or block translation

Question 14

Where do miRNAs bind?

Answer 14

complementary sequences in the 3’ UT end of mRNA

Question 15

What mechanism do miRNAs use?

Answer 15

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

Question 16

True or false?

miRNAs change their expression profile in disease states

Answer 16

true

ex: miR-29 is decreased in heart disease, miR141 is elevated in prostate cancer

Question 17

Explain how changes in miRNA expression are causative of disease and responsive to disease

Answer 17

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

Question 18

Molecular chaperonnes, protein kinases, glycosylation, partner proteins are all involved in what?

Answer 18

protein modification

Question 19

Why are most molecular chaperones heat shock proteins?

Answer 19

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

Question 20

In regards to regulation by protein degradation, how does ubiquitin work?

Answer 20

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

Question 21

Another way ubiquitin works is by the addition of a protein with a degradation signal to ubiquitin ligase. What happens after this?

Answer 21

ubiquitin chain is added to lysine side chain on protein and the chain is recognized by proteasome

Question 22

In regards to specificity of the ubiquitin complex, how many different E1, E2 and E3 proteins are there?

Answer 22

E1: 1
E2: 30
E3: hundreds

Question 23

Glucocorticoid cortisol expression in response to stress - increase blood sugar - aid in fat -, protein, cab metabolism - diurnal etc. is a example of what?

Answer 23

coordinated gene expression

Question 24

In regards to specialization of blood cells, heamtopoietic pluripotent stem cells have two options. What are they?

Answer 24

myeloid lineage or lymphoid lineage, meaning they can make a RBC, megakaryocyte, macrophage, or T or B cells

Question 25

True or false?

methylation is inherited

Answer 25

true; genomic imprinting is based on DNA methylation

Question 26

Define genomic imprinting

Answer 26

differential expression of genetic material depending on the parent of origin

Question 27

Regulation of expression of gene activity without altering gene structure is called what?

Answer 27

epigenetics

Question 28

Prader Willi syndrome is a genomic imprinting disorder. What causes it? What is its presentation?

Answer 28

parental deletion on chromosome 15 inherited from father; Stage one presentation: poor sucking. Stage two: early childhood obesity

Question 29

What is paternal gene expression?

Answer 29

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

Question 30

Why does dosage compensation occur?

Answer 30

so number of genes expressed from X chromosome is equal in males and females

Question 31

True or false?

In females, one of the X chromosomes is inactive.

Answer 31

true; called a barr body