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Molecular Biology > Control Of Gene Expression II > Flashcards

Control Of Gene Expression II Flashcards

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1
Q

How can RNA splicing be negatively regulated?

A

By repressor moleculs that prevents splicing machinery access to splicing sites.

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2
Q

How can RNA splicing be regulated positively?

A

By activating molecules that recruit and help direct splicing machinery.

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3
Q

How do mRNAs leave the nucleus?

A

Through pores.

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4
Q

How do mRNAs travel to their destinations?

A

By using cytoskeletal motors. Anchor proteins hold mRNA in place.

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5
Q

What happens to RNA that is not trapped?

A

It is degraded

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6
Q

What is found on the end of mRNA that contributes to its stability?

A

A poly-A tail.

It acts as a timer; once reduced to 25 nucleotides, two pathways converge to degrade mRNA.

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7
Q

Where is exposed mRNA degraded from?

A

The 5’ end. The 5’ cap serves to protect RNA from RNA degrading enzymes.

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8
Q

Regulation by RNA stability:

  1. MRNA degraded from 3’ end through poly-A tail and into coding region.
A

:-)

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9
Q

What is the control of RNA involved in?

A

Iron metabolism

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10
Q

Iron transport from the intestine to bone marrow involves the discovery of what?

A

Many proteins that have been recently discovered.

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11
Q

What is the pathway of the iron cycle?

A

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.

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12
Q

What is the function of ferritin?

A

It binds thousands of Fe3+ molecules and is found in most cells.

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13
Q

What is hemosiderin?

A

Granules of the ferritin protein.

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14
Q

In what organs is excess iron mainly stored by?

A

Liver

Lungs

Pancreas

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15
Q

What occurs during iron starvation?

A

A decrease in ferritin mRNA.

Cells must transport iron into cells, and transferrin receptor is made in order to do so.

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16
Q

What occurs during excess iron?

A

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).

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17
Q

What does mRNA regulation involve?

A

Iron responsive elements (IREs) and iron responsive regulatory protein (IRP) aconitase.

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18
Q

Where does IRP bind to IRE?

A

At 5’ ferritin mRNA (this causes no ferritin to be produced)

At 3’ transferrin receptor mRNA (transferrin receptor is made).

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19
Q

What are microRNAs?

A

Regulatory RNAs that regulate messenger RNAs.

These are noncoding RNAs that silence the expression of specific mRNA targets.

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20
Q

Where to miRNAs bind?

A

To complementary sequences in the 3’ UT nd of mRNA.

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21
Q

What is the function of miRNAs?

A

They degrade RNA or block translation.

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22
Q

How do microRNAs affect gene activity?

A

They repress gene activity.

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23
Q

What are the components of the RNA-induced silencing complex (RISC)?

A

MicroRNA, argonaute and other proteins.

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24
Q

What does miRNA base pair with?

A

MRNA

25
Q

What does microRNA cleave?

A

RNA.

It also shuts down its expression.

26
Q

Each miRNA can repress ___ of mRNAs.

A

Hundreds.

MiRNA binding sites are widespread, and 1 miRNA can affect a whole biological program.

27
Q

What happens to miRNA during disease states?

A

MiRNAs change their expression profile.

For example, certain miRNAs can be elevated in stroke or cardiovascular disease.

28
Q

Are the changes in microRNA expression causative of disease or responsive to disease?

A

Yes!

Causative: miRNAs likely hav mutations that cause diseases.

Responsive: increased miRNA expression down regulates genes in response to disease to limit severity.

29
Q

What is a disease that is indicivative of the causative nature of miRNAs?

A

Tourettes syndrome.

MiRNA involvement was found with 1 form of Tourette’s Syndrome.

A change in the recognition sequence on target SLITRK1 mRNA -> increased miRNA binding.

30
Q

How does miRNA cause Tourette’s Syndrome?

A

MiR-189 binds more efficiently to target sequence in 3’ UT of SLITRK1 gene and decreases SLITRK1 expression. This leads to Tourette’s syndrome.

31
Q

What helps proteins to fold into their 3D conformations and hence become functional?

A

Molecular chaperones

32
Q

What are some requirements of protein folding?

A

Folding and cofactor binding

Covalent modifications by glycosylation, phosphorylation, etc.

Binding to other protein subunits

Mature functional protein.

33
Q

Many molecular proteins are heat shock protein, which are synthesized in dramatic amounts when temperature is raised. Why is this so?

A

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.

34
Q

What is important for the regulation of proteins by degradation?

A

The proteasome.

35
Q

What is the function of the proteasome?

A

It controls protein activity by choosing what proteins are around.

It removes misfolded proteins.

The proteasome is an apparatus that destroys aberrant proteins.

36
Q

What is the function of ubiquitin?

A

It removes unfolded or abnormal proteins.

It does so by linking cysteine side chains to E1 - E3 enzymes, and primes proteins for destruction.

37
Q

What is the side chain on a protein that ubiquitin binds to?

A

A lysine side chain.

38
Q

What is the specificity of a proteasome?

A

It is specific for two E1 ubiquitin activating enzymes and 1 proteasome but 30-40 ubiquitin conjugating enzymes and hundreds of E3 accessory proteins.

39
Q

What are proteasome inhibitors used to treat?

A

Multiple myelomas (cancer of plasma cells)

40
Q

The chamber in a proteasome has 3 proteolytic sites. Bortezomid interacts with 1 protelolytic site. What does it specifically inhibit?

A

Myeloma cells

41
Q

How is ubiquitin ligase activated?

A
  1. Phosphorylation by protein kinase.
  2. Allosteric transition caused by ligand binding.
  3. Allosteric transition caused by protein subunit addition.
42
Q

What are the steps in the activation of a degradation signal?

A
  1. Phosphorylation by protein kinase
  2. Unmasking by protein dissociation.
  3. Creation of destabilizing N-terminus.
43
Q

What are other controls of gene expression?

A
  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.
44
Q

What can the expression of critical regualtory proteins cause?

A

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.

45
Q

What is the consequence of gene control?

A

It can produce many types of cells.

46
Q

What are two major fates of blood cells?

A

HSC (hematopoietic stem cell)

HPC (hematopoietic pluripotent stem cell)

47
Q

What can DNA be regulated by?

A

Proteins.

DNA itself can also be covalently modified.

48
Q

Where does methylation of cytosine occur?

A

At CG sequences.

49
Q

True or false: methylation is inherited, and DNA methylation of a parent strand serves as a template for a daughter strand.

A

True

50
Q

What is genomic imprinting?

A

Differential expression of genetic material depending on the parent of origin.

51
Q

What is epigenetics?

A

Regulation of expression of gene activity without altering gene structure (e.g. Methylation).

52
Q

What is genomic imprinting based on?

A

DNA methylation

53
Q

What are examples of genomic imprinting disorders?

A

Prader Willi syndrome.

It is caused by paternal deletion on chromosome 15.

54
Q

In genomic imprinting disorders, what is the significance of paternal gene expression?

A

Genes in the chromosomal region are not expressed when inherited from Mom, but are expressed when inherited from Dad.

55
Q

What is the purpose of dosage compensation?

A

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.

56
Q

In development, one X chromosome is inactivated in femals. When is it activated?

A

During gamete cell formation.

57
Q

What is the X-inactivation center?

A

A region where inactivation of an X chromosome starts and spreads.

58
Q

What is the function of alternative splicing?

A

It produces different forms of proteins from the same gene.

RNA transcripts are spliced differently.

Molecular Biology (12 decks)

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