miRNAs and Developmental Canalisation Flashcards

1
Q

Canalisation

A

“Robustness”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How many genes are in the human genome?

A
  • urban myth = 100,000 (actually c40,000)
  • 21,306
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Why approximate?

A

Counting conundra
- pseudogenes
- small ORFs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Genes produce functional

A

ncRNA (>20,000)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

HOTAIR

A
  • long ncRNA
  • several one
  • recruits H3K27me3 on Hox
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

HOTTIP

A
  • long ncRNA
  • several kb
  • recruits H3K4me3 on Hox
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

miRNAs

A
  • c22nt
  • 100s/1000s / species
  • vibe mRNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

miRNA cleavage

A
  • in plants and animals
  • perfect match
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

MiRNA blockage

A
  • animals
  • approximate match
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

miRNA summary

A

1) miRNA transcription
2) folds into c70nt pri-miRNA hairpin
3) Drosher and Pasha: pre-miRNA
4) nuclear export
5) DICER
6) RISC complex takes up strand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Why use miRNAs for I regulate gene activity during development?

A
  • faster than transcriptional control
  • RNA half-life; temporary, highly localised control
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Paradoxical miRNA findings

A
  • some are highly conserved
  • v. few are lethal mutants
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Finding the targets:

A
  1. Sequence matches (3’UTR) ; false hits
  2. Introduction (look for <RNA) ; indirect effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Human miRNA introduction in HeLa cancer cells

A
  • muscle expressed miRNA1 suppresses no muscle genes
  • brain expressed miRNA124 suppresses non-brain genes
  • microarray; c100 genes go down for each miRNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

miRNA non cell-autonomous behaviour

A

Weed out stochastic / polymerase / chromatin errors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

miRNA-9A

A
  • non-lethal mutant; changes no of sensory bristles in larva, adults
  • subtle differences, controlling precision
  • expressed in Drosophila SOPs
  • Senseless also expressed here; layers of regulation
17
Q

SOPs

A

Sensory organ precursors

18
Q

Senseless

A

TF

19
Q

Mode 1

A
  • express in different cell to targets
  • keeps leaky transcription down
20
Q

Mode 2

A
  • express in same cells as targets
  • precision
21
Q

Development

A
  • probabilistic
  • stochastic variation
  • liable to biochemical error
  • underpinned by Brownian motion
22
Q

Does canalisation allow the evolution of complexity in Animalia?

A
  • miRNA increases the correlation between genotype and phenotype
  • cuts out evolutionary “noise”
  • increases trait heritability
  • speeds up evolution
  • selection works on phenotypes, but genotypes are inherited
23
Q

Does miRNA no correlate with complexity?

A
  • hard to test: incomplete dataset
  • increased early in evolution
  • lots @ bilaterian base: Cambrian explosion
  • hints!