Day 15, Lecture 4 (Sept 13): Molecular and Cellular Networks

Question 1

Most Cellular functions are regulated via

Answer 1

Question 2

All the places in Red are spots that if a mutation is to occur you could get cancer

Question 3

Question 4

Nonsense mediated decay (NMD)

Answer 4

Question 5

____ nonsense mutation result in effective nonsense mediated decay (NMD) while _____ mutations lead to ineffective NMD

Answer 5

• Primal nonsense mutations result in effective NMD while distal nonsense mutations (e.g. in the last exons) lead to ineffective NMD

Question 6

Proximal nonsense mutations often result in ____ while distal mutation result in

Answer 6

• Proximal nonsense mutations lead to loss of function due to nonsense mediated decay
• While Distal mutations result in truncated proteins
  
  • Dominant negative effects

Question 7

What happens if a nonsense mutation is just proximal to an EJC

Answer 7

The signal does not work very well and the protein will most likely still be secreted even though it is truncated

Question 8

Iron transporter is regulated by

Answer 8

• levels of iron
  
  • RNA-binding protein regulates Fe transport during Fe deficiency

Question 9

• Iron is stored by ___, which is required at ___ Fe levels .

Answer 9

Question 10

_______ absorb Fe and is required at ____ Fe levels

Answer 10

Question 11

Expain how Transferrin receptor and Ferritin are regulated

Answer 11

• Iron Response element (hairpin)- binding protein IRE-BP is activated by decreased levels of Fe
• IRE-BP binds to the Iron Response Hairpin located on the mRNA for both ferritin and transferrin receptors (TfR)
• The difference in action is based on the location of the binding
  
  • In ferritin mRNA IRE-BP binds to the 5’ UTR thus blocking the ribosome and inhibiting translation initiation
  • In transferrin mRNA IRE-BP binds to the 3’UTR thus protecting mRNA from degradation

Question 12

microRNA (miRNA) regulation of gene expression

Answer 12

• Short RNA molecules can degrade transcripts (post-transciptional gene regulation) or induce heterochromatin (transcriptional gene regulation)

Question 13

miRNA Post-Transcriptional regulation of gene expression

Answer 13

• Pre-miRNA is clipped into shorter sections by dicer to form miRNA
• This and Ago+ other RISC proteins combine to make single stranded miRNA
  
  • this then acts on the its subsequent RNA sequence to lead to degradation

Question 14

What is the difference between siRNA and miRNA

Answer 14

• miRNA (endogenous)
• siRNA (exogenous)

Question 15

miRNA Transcriptional regulation (heterochromatin formation)

Answer 15

• Pre-miRNA is clipped into shorter segments by dicer to form miRNA
• miRNA combines with Ago and other RITS proteins (note that this is RITS and not RISK, which is the Post-transcriptional protein)
• goes into the nucleus and clips onto DNA segement
• recruits HMT and DNMT and leads to histone methylation and DNA methylation (thus forms heterochromatin) to inhibit transcription

Question 16

DNA double-strand breaks can induce _______ arrest and apoptosis

Answer 16

G1/S

Question 17

Question 18

Explain the mechanism/pathway for double stranded breaks cell cycle inhibition

Answer 18

• A double strand break leads to the phosphorylation of ATM dimer (inactive)
  
  • this leads to a phosphorylated ATM monomer (active)
• Once activated ATM does 2 things:
  
  • It recruits proteins to fix the double stranded break (MRE11, RAD50, Nibrin) and BRCA1
  • Phosphorylates check 2
• Check2 phosphorylated (active) is now able to phosphorylate p53 thus making it stable and active
• p53 leads to cell cycle arrest at G1/S and apoptosis

Question 19

Question 20

Question 21

Question 22