Long non-coding RNAs

Question 1

What are some examples of long noncoding RNA?

Answer 1

• antisense RNAs
• pseudogenes
• LUC7L
• HOTAIR

Question 2

What are antisense RNAs?

Answer 2

• RNA sequences that are complimentary to sense RNA
• can bind to sense RNA and regulate its gene expressoin

Question 3

How many human genes have antisense RNAs?

Answer 3

20%

Question 4

What suggests that antisense RNAs have a regulatory role?

Answer 4

they are usually expressed coordinately with sense RNA

Question 5

What is sense-like vs sense

Answer 5

sense means the two have complete complimentary and can bind one another fully
sense like means the antisense bears resemblance or shares sequence characteristics with the sense RNA without being complementary

Question 6

What role may antisense RNA have in the FGF2 gene?

Answer 6

• FGF2 involved in angiogenesis and proliferation
• antisense RNA exons 4 and 5 have high homology with the sense transcript
• studies suggest some kind of RNA interference mechanism by which the antisense binds to the sense to form dsRNA which is not read by ribosomes

Question 7

How does antisense RNA regulate KLHL1?

Answer 7

• involved in actin polymerisation
• overlapping antisense RNA has an expanded CUG repeat
• this inhibits the splicing of KLHL1 or increases its binding site for regulatory factors

Question 8

What are pseudogenes?

Answer 8

• non-coding counterparts to coding genes that have lost their function over time in evolution
• some play a role in regulating their functional counterparts

Question 9

Give an example of a pseudogene regulating a functional gene to increase its transcription

Answer 9

• Markorin1 is a transcriptional regulator and E3 ligase that regulated p21 and p53
• stabilised by pseugogene Makorin-P1
• P1 transcripts can sequester transcriptional repressors or RNA degrading proteins from Markorin1 to increase its transcription and expression

Question 10

Give an example of a pseudogene regulating a functional gene to decrease its transcriptoin

Answer 10

• the pseudogene of neural nitric oxide
• forms a duplex with the functional gene RNA
• prevents or decreases its transcription

Question 11

What is LUC7L?

Answer 11

• normally a coding gene involved in mRNA splicing
• deletion of its polyadenylation signal allows it to pass termination and become a long non-coding RNA that leads to increased methylation of alpha globin genes and alpha-thalassemia
• not enough alpha-globin produced which is used to make hemaglobin

Question 12

Give an example of antisense RNA being involved in genomic imprinting

Answer 12

• in IGFR imprinting
• on the paternal allele the antisense IGFR is transcribed and the gene is off

Question 13

What is tsix?

Answer 13

• xist antisense RNA that can lead to X activation
• can prevent the binding of factors that stabilise Xist and let it associate with chromatin
• can prevent transcription and accumulation of Xist transcripts
• can open up the chromatin to allow binding of activating factors

Question 14

Give an example of a non-coding RNA in cancer

Answer 14

• HOTAIR reprograms chromatin to promote cancer metastasis
• high levels in hox clusters in breast cancer show lower survival
• recruits PRC2 which leads to hypermethylation of H3K47 and silencing of metastasis suppressor genes