Gene Expression II Test Two Flashcards
What is one way to produce different forms of protein from the same gene?
Alternative splicing. Splicing RNA transcripts differently
Describe positive and negative control of alternative splicing?
Negative control through a repressor which prevents the splicing machines to access the splice sites. Positive control is through an activator which recruits and directs splicing machines.
Explain what is meant by poly-A tail timer.
The tail is gradually shortened by exonucleases and once it hits a certain point, 25 nt, it signals for degradation.
What are IRE’s and IRP’s? (Dr. Whites Ex ?)
Iron responsive elements are recognition sites on mRNA for binding. Iron responsive regulatory proteins are proteins tha bind to mRNA
How do mRNA’s travel to cytoplasm?
They use cytoskeletal motors to travel through nuclear pores.
What causes destruction of the 5’cap?
Degradation through the poly A tail into the coding region of the gene or decapping exposing the 5’ end.
What does Ferritin mRNA do?
Helps with storage of iron. Binds thousands of Fe3+ molecules and is found in most cells
What does TfR mRNA do?
helps with iron absorbance. Has erythroid precursors in bone marrow
Describe what occurs during iron starvation.
Cells no longer need to store iron it needs to be circulated. There is a decrease in Ferritin through IRP binding IRE of ferritin mRNA and an increase in TfR mRNA through IRP binding IRE at 3’ end transferrin receptor.
What happens when there is excess iron in the body?
Iron no longer needs to be circulated but stored. There is less TfR mRNA and more Ferritin mRNA produced so more storage occurs. The IRP binds to iron to inactivate it and ferritin is made with no suppression.
How do IRP’s regulate iron storage and circulation?
They can bind to the IRE at the 5’ ferritin mRNA end to block translation-no ferritin made. They can also bind IRE at the 3’ transferrin receptor on mRNA- make receptor for transferrin stabilizing the mRNA
What occurs if IRP does not bind to hte 5’ ferritin mRNA or the 3’ TfR mRNA?
If IRP isn’t bound at 5’ mRNA gets made and ferritin is made If doesn’t bind IRE at 3’ end no transferrin receptor is made.
Iron Starvation:
IRP binds ferritin and TfR mRNA –> no ferritin, TfR is made
Iron Excess:
IRP does NOT bind–> Ferritin is made, no TfR made
What do miRNA’s do?
Degrade RNA or block translation. binds to the complementary sequences in the 3’ UTR of mRNA. RNA with hairpin loop. Each miRNA can repress humdreds of mRNA’s and can change expression in disease states
Are changes in miRNA expression causative or responsive to disease?
Both. miRNA;s have mutations that likely CAUSED the disease. Increase in miRNA expression down regulates genes in RESPONSE to disease to limit severity.
Describe miRNA involvement with Tourette’s syndrome.
Change in the recognition sequence on the target mRNA increased the miRNA binding it binds efficiently to decrese the expression of SLITRK1 gene leading to tourettes.
What destroys proteins?
Proteasome
What is a proteosome?
A hollow chamber that degrades proteins, it has six ATP dependent active sites. Recognizes Ubiquinated proteins
What does Bortezomid do?
Interacts with one of the proteolytic sites on proteosomes it reversibly inhibits it. It can prevent apoptosis. It triggers apoptosis in neoplastic cancer cells, specifically myelomas.
Describe genomic imprinting and how it can lead to disease. (Dr. Whites ex ?)
Genomic imprinting is when expression of a particular gene is only expressed from one set of parents even though both are present. If there is a deletion of one set of alleles there will be presence of disease because the other allele is silent due to methylation. Imprinting is a form of epigenetics.
Describe the RNA control of ferritin mRNA and transferrin receptor mRNA under conditions of excess iron. (Dr. Whites ex ?)
If there is an excess of iron in the body the IRP will bind to the IRE at the 5’ end of the ferritin mRNA. This binding will allow ferritin to be translated. The IRP will not bind the IRE at the 3’ end because that would cause TfR mRNA to be produced which would circulate iron.
Describe the RNA control of ferritin mRNA and transferrin receptor mRNA under conditions of iron starvation. (Dr. Whites ex ?)
More iron is needed in the body and less needs to be stored therefore IRP will bind to the 3’ end of the transferrin receptor mRNA increasing stability to translate the Transferrin receptor IRP will not bind to the IRE at the 5’ of ferritin mRNA as that will cause a blockage of translation and no ferritin will be made because storage is not needed.
What are four types of gene expression controls?
- Coordinated expression of genes 2. Decision for specialization 3. Methylation and genomic imprinting 4. X chromosome inactivation
