Module 6 - Part 2

Question 1

Non-coding RNA (ncRNA)

Answer 1

• 70-90% of the genome codes for
  >200nt
• long non-coding RNA
• 15900
  <200nt
• small non-coding RNA
• 9894

Breakdown:
- pseudogene 14825
- non-coding 25794
- protein coding 19814

Question 2

Xist

Answer 2

X-inactivation specific transcript
- x-inactivation centre (XIC) on the x-chromosome
- >17000nt long
- acts as a protein scaffold

Question 3

Tsix

Answer 3

The antisense transcript of Xist
- another IncRNA (long non-coding)
- encoded on the antisense DNA strand
- expressed Xa at the XIC and blocks Xist from functioning on Xa

Question 4

3 Ways of Blocking Xist from functioning on the active X (Xa)

Answer 4

1. Transcriptional interference (blocks transcription)
2. Tsix masks Xist RNA domain
3. Tsix enhances Xist RNA degradation (via RNAse)

Question 5

mircoRNAs

Answer 5

• mature miRNAs are short (17-25nt) single stranded transcripts that regulate translation miRNA processing

Question 6

Translation miRNA processing

Answer 6

1. primary microRNA (pri-miRNA) 1000nt
   - contain hairpin(s) that includes mature miRNA transcript
2. drosha processes pri-miRNA into precursor-miRNA (pre-miRNA)
3. pre-miRNA exported to cytoplasm where it’s cleaved by Dicer - yield double stranded miRNA
4. RNA induced silencing complex (RISC) incorporates that mature miRNA-bound
5. RISC interacts w target mRNA in one of 2 ways to silence gene expression

Question 7

Two ways of silencing gene expression in miRNA

Answer 7

1. perfect pairing: allows for mRNA cleavage & degradation (no mRNA = no translation)
2. imperfect pairing: prevents binding of ribosomal subunit (mRNA present but translation blocked)

Question 8

What is PTSD

Answer 8

Post traumatic stress disorder
- psychiatric disorder that can arise in people who have experienced a traumatic event

Question 9

PTSD subunits

Answer 9

• re-experiencing
• avoidance
• negative changes in mood and thinking
• changes in physical and/or emotional reactions

Question 10

PTSD Statistics

Answer 10

50-85% of population will go through a traumatic event but only 7-8% will develop PTSD

Question 11

What determines PTSD risk?

Answer 11

Environment
- can arise due to environmental triggers/trauma
- originally thought to be the sole cause
Genetics
- twin studies suggests genetic variation is implicated in PTSD development (H2 of 0.3-0.7)
- genetic & GWAS have not identified reliable/robust genetic variants for PTSD
- epigenetics play a role

Question 12

Stress response team (eg. flight or fight response)

Answer 12

1. hypothalamus secretes
2. CRH (corticotropin-releasing hormone) which is received by
3. pituitary gland, which releases
4. ACTH adrenocorticotropic hormone which is received by
5. adrenal gland (atop of kidneys) which releases
6. cortisol (stress hormone)
7. hypothalamus responds to level of cortisol (binding to glucocorticoid reception = negative feedback loop = shut down stress response)

Question 13

Role of NR3C1 in PTSD

Answer 13

• many stress response genes are epigenetically modified in response to trauma
• glucocorticoid receptor (NR3C1) exhibits elevated levels of DNA methylation
• hypermethylation of NR3C1 observed in individuals with PTSD (can’t shut off stress response)

Question 14

Epigenetic in transgenerational trauma

Answer 14

Evidence of transgenerational epigenetic and behavioural changes in animal models
Harder to study in humans (family may be subject to similar trauma and hard to separate trauma from environmental influence)
- mouse study
- mom and offspring were separated at birth = trauma
- untraumatized female mates with traumatized males
- offspring show epigenetic & behavioural changes without having experienced trauma
- carried out for 6 generations