Craniofacial abnormalities

Question 1

Neurocristopathies

Answer 1

Neurocristopathies are congenital malformations arising from defects in the development of neural crest cells

Question 2

Mutations in genes encoding ribosome proteins or involved in ribosome production can cause at least two related craniofacial abnormalities

Answer 2

Treacher- Collins syndrome and Diamond Blackfan Anemia.

Question 3

Mutations in genes encoding ribosome proteins or involved in ribosome production can cause at least two related craniofacial abnormalities

Answer 3

Treacher- Collins syndrome and Diamond Blackfan Anemia.

Question 4

At the cellular level, abnormal neural crest cell development can result in…?

Answer 4

• not enough cells being formed, disruptions in cell migration, and failures of cells to produce the appropriate gene products necessary for differentiation

Question 5

Ribosome production

Answer 5

Nucleoli form around NORs that contain tandem repeats of the 45S rDNA sequence (18S, 5.8S, 28S) which is transcribed by RNA pol I (occurs in the nucleolus)
the 5S sequence is transcribed by RNA pol III (occurs on chromosome 1)

Question 6

What are ribosomes and what are they made out of?

Answer 6

large macromolecular assemblies of proteins with ribosomal RNA (rRNA). Each ribosome contains 4 rRNAs plus around 85 different ribosomal proteins. These assemblies are divided into two subunits, the 60S large subunit and the 40S small subunit, which are built separately.

Question 7

Where can mature ribosomes be found? free in the cytoplasm or attached to the endoplasmic reticulum

Answer 7

Mature ribosomes can be found free in the cytoplasm or attached to the endoplasmic reticulum

Question 8

What is the role of the ribosome?

Answer 8

translate RNA into protein

Question 9

Describe 45S rRNA transcription

Answer 9

1. UBF bings to the UCE and core elements, recruits SL1
2. UCE and core elements are brought together
3. RRN3/TIF-1A (transcription initiation factors) bind
4. Pol I binds and transcription begins
5. UBF and SL1 remain in place, loading more POL 1

Question 10

Describe 45S rRNA transcription

Answer 10

1. UBF bings to the UCE and core elements, recruits SL1
2. UCE and core elements are brought together
3. RRN3/TIF-1A (transcription initiation factors) bind
4. Pol I binds and transcription begins
5. UBF and SL1 remain in place, loading more POL 1

Question 11

Describe the promotor region of the 45S rRNA

Answer 11

Promoter: no TATA box, UCE at -200 to -107, Core promoter (CP) at -45 to +20

Question 12

What is SL1?

Answer 12

TBP (TATA binding protein) plus three TAFs

Question 13

What transcription factors bind in 45S rRNA transcription?

Answer 13

RRN3/TIF-1A

Question 14

What transcription factors bind in 45S rRNA transcription?

Answer 14

RRN3/TIF-1A

Question 15

What pathway specifically monitors the process of rRNA transcription?

Answer 15

The nucleolar stress response, which works through p53

Question 16

How does the nucleolar stress response normally operate when everything is fine?

Answer 16

The MDM2 protein binds to p53 and ubiquitinylates it with an E3 ligase domain at its C terminus. This leads to the degradation of p53 by the proteosome.

Question 17

What happens when ribosomal rRNA production is not keeping up with ribosomal protein production?

Answer 17

unincorporated ribosomal proteins accumulate. These will bind to the central acidic region of MDM2 and prevent it from ubiquitinylating p53. Hence, p53 levels build up and stimulate the expression of p53 response genes, which triggers apoptosis of the cell.

Question 18

What do you expect happens to p53 if it is ubiquitinylated?

Answer 18

p53 will be degraded by the ptoreosome