1: L9

Question 1

2 key forms for RNAs

Answer 1

• miRNAs

* Long noncoding RNAs

Question 2

Describe miRNA

Answer 2

• Small non-protein coding RNAs: 21-22nt long and double-stranded

Question 3

Where are genes for miRNA found

Answer 3

often in introns (gets spliced), or intergenic (between protein coding genes)

Question 4

2 functions of miRNA

Answer 4

degrad, block

• Recognise targets in 3’ untranslated region (UTR) of mRNAs by sequence-specific binding
o If the match is perfect: degrade mRNA target (regulates gene as never made into protein)
o If the match is imperfect: Inhibit translation (i.e. making protein, some is made by not as much protein is made)
• Fine tunes gene expression

Question 5

How many targets does miRNA have

Answer 5

• miRNA can have multiple target mRNAs – some being degraded others translationally inhibited

Question 6

Name 2 example miRNA

Answer 6

Mir7

Mir200 Fam

Question 7

Describe Mir7

Answer 7

miRNA
• Down-regulated in cancer
• Plays a role in preventing invasion and migration in melanoma
o // Overexpression of mir7= less migration

Question 8

Describe mir200

Answer 8

• Mir200 miRNAs are downregulated in epithelial to mesenchymal transition
• Mir200 suppresses ZEB1 and ZEB2 (transcriptional repressors of e-cadherin > leading to high e-cadherin and a sustained epithelial phenotype)

Question 9

Describe mir200 + SEB pathways in normal/cancer cells

Answer 9

• Normal cell = mir200 > supress ZEB1 and ZEB2= high cadherin
• Cancerous = low mir200> high ZEB = low ecadherin
  • Allows cells to break apart and move through epithelium (> mesenchymal cells)

Question 10

what is a long-noncoding rna

Answer 10

RNA >200 nucleotides in length that does not contain obvious protein coding potential

Question 11

What is lncRNA overarching theme

Answer 11

ontrolling gene expression

Question 12

Where do lncRNA usually act + what is cis/trans

Answer 12

act nearby to their transcription site
o often affecting the regulation of neighboring protein-coding genes
- Cis= locally, trans, float through nucleus/cyto and do something elsewhere away from gene that made it

Question 13

4 archetypes of lncRNA + example of each

Answer 13

Signals- linc-p21
Decoys- PANDA
Guide- XIST
Scaffold- NEAT1

Question 14

Describe Signal archetype of lncRNA

Answer 14

lncRNA expression = reflect combinatorial actions of transcription factors (colored ovals) or signaling pathways to indicate gene regulation in space and time (quicker than a protein).

Question 15

Describe DECOY archetype of lncRNA

Answer 15

• As Decoys, lncRNAs can titrate away transcription factors (take away) and other proteins away from chromatin, or titrate the protein factors into nuclear subdomains.

Question 16

Describe GUIDE archetype of lncRNA `

Answer 16

• As Guides, lncRNAs can recruit chromatin modifying enzymes to target genes, either in cis (near the site of lncRNA production) or in trans to distant target genes.
• Can recruit and guide epigenetic factors

Question 17

Describe SCAFFOLD archetype of lncRNA

Answer 17

lncRNAs can bring together multiple proteins to form ribonucleoprotein complexes. The lncRNA-RNP may act on chroma-n to affect histone

• The lncRNA scaffold could also be structural: stabilizing modifications.
• nuclear structures or signaling complexes

Question 18

What does PANDA do

Answer 18

prevents transcription of genes that promote apoptosis

Question 19

Describe XIST

Answer 19

• Acts as a signal and guide
  o Xist (X-inactive specific transcript): found on the X chromosome in placental mammals
  o essential for X-inactivation (process of females silence one of their X- chromosomes)

Question 20

Describe HOTAIR

Answer 20

o HOTAIR (HOX An-sense Intergenic RNA) is found in the HOX gene cluster
o HOX genes are vital for patterning in the embryo (head to tail axis)
o HOTAIR represses genes by changing the epigenetic state and inducing heterochromatin
o HOTAIR is upregulated in many cancers and is correlated with metastasis and death

Question 21

Describe NEAT1

Answer 21

• NEAT1 was the first lncRNA shown to be a structural scaffold for a subnuclear body: paraspeckles
• Bound to form paraspeckles
• NEAT1 makes paraspeckles under stress conditions and alters gene regulation by sequestering proteins and RNAs