lncRNAs Flashcards
how long is the Xist transcript
17kb spliced polyadenylated transcript
How many genes have an antisense RNa
approximately 20%
Nme some genes that have antisense RNAs
WT1 and n-myc however antisense RNAs dont control their protein levels
What is Msx1
It is muscle like homeobox 1
It has an antisense RNA and the msx-1 levels are regulated by antisense trasncripts
Which part of msx1 does the antiense strand overlap
exon 2
What do the different isoforms of cerbA do
isorform 1) encodes the thyroid hormone receptor
isoform 2) inhbits 3 action
What does the antisense of c-erbA do
It inhibits splicing and therefore leads to regulation of the protein isofrom balance
What is the sense transcript of SCA8 and what is thought tot be involved in
KLHL1 –> thought to be involved in the cytoskeleton organisation in brain cells
What is the defect in spinocerebellar ataxia
Expansion of the CUG repeat in SCA8 –> may interfere with splicing or sequester TF
sWhat are pseudogenes
Defective copies of genomes (mutated ORF) that have accumulated during evolition
approximately 20000 in the human genome
Give an example of a pseudogene positively reuglated experssion of the normal gene
The makorin-p1 pseudogene positively regulated makrin short form gene possibly as the pseudogene may instead attract regulators to degrade it or the transcriptional suppressors may instead suppress the pseudogene
Give an example of negative regulation by a pseudogene
An antisense trasncript in a pseudogene of the neural nitric oxide synthase protein may suppress it
Describe how HBA2 is silenced by LUC7 in alpha thalassaemia
LUC7L is downsteam of HBA2 and the transcript is read in the opposite direction
In alpha-thalassaemia the polyA signal for LUC7L is delted
Hence you get read throguh transcription of LUC7L which extends downsteadm of the HBA2 locus
this leads to hypermethylation of the HBA2 promoter causing epigenetic silencing
Give some example of imprinted genes with anti-sense RNAs
AIr
KCNG1Ot1
Xist
What happens with deletion of ICE/AIR
Get bi-allelic transcription of IGF2
What allele is air transcribed from
Air is transcribed from PATERNAL ALLELES ONLY –> leads to silencing of igf2 and slc genes
In maternal alleles methylation of ICE turns of Air and the Igf2r and Slc genes are transcribed
What is Tsix
It is an antisense transcript of Xist which if present can block Xist function and lead to X activation
How might Tsix work
Prevents binding of factors needed to stabilist Xist
Prevents efficient transcription of the Xist gene
May bind to the putative blocking factors somwehere in teh Xist 3’ region
Enables the bidning of develpmentally regulated factors to the Xic region
What lncRNA in cancer increases metastatic breaset cancer
HOTAIR
How does HOTAIR increases the risk of breast cancer metastasisng
Complexes with PRC2 and causes it to get new targets and shuts down lots of genes
What are microsatellite repeats
They are short repeats (2-6bp) polymorphic repeat squences
What is the repeat expansion in myotonic dystropgy 1
CUG repeat expansion in the 3’ UTR of the DMPK
What is the repeat expansion in myotonic dystrophy 2
CCUG repeat expanision in the ZNF intron 9
What are the characteristics of lncRNAs
200nt- 100kb, lack an ORF
RNA Pol II Transcribes them
Generally lower expression than coding genes
Give an example of some imprinted lncRNAs
H19
Xist
What 2 lncRNAs have roles in metastasis
HOTAIR
MALAT1
What is MALAT1
Metastasis Associated Lung Adenocarcinoma Transcript
Higher levels in cancers and poor prognsosis
Transcript processes to produce a short tRNA and a MALAT1 transcript
Implicated in cell mobility –> inhibiting reduced the invasive potential of cervical cancer cells
What lncRNA can stimulate p53
MEG3 –> often high level in brain and pituitary but undetectable in brain cancer
What is HULC
a miRNA that is highly upregulated in liver cancer –> acts as a sponge to miRNA 372
What is ANRIL and how does it fucntion
Antinsense noncldoing RNA in the INK4 locus
ANRIL can mediate silencing of the INK4b-ARF-INK4a locus by recruiting PRC1/2
