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Advances in Medicine > Non-coding RNA > Flashcards

Non-coding RNA Flashcards

1
Q

What are the components of RNA structure?

A

Nitrogenous base
Pentose Sugar (Ribose)
Phosphate group

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2
Q

Name some of the secondary structures of RNA

A 
Single Strand
Double Strand
Single-nucleotide bulge
Three nucleotide bulge
Hairpin loop
Symmetric internal loop
Asymmetric internal loop
Two-stem juntion (coaxial stack)
Three-stem junction
Four-stem junction
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3
Q

Name some tertiary structures of RNA

A

Pseudoknot
Kissing hairpins
Hairpin loop-bulge contact

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4
Q

Why is alternative splicing useful?

A

It generates multiple mRNAs and proteins from one protein-coding gene

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5
Q

What are the properties of RNA?

A

Both encode sequence information and possess great structural plasticity
Can directly interact with DNA and other RNAs
Highly structured RNA can also provide docking sites for binding proteins
Compact size and significant specificity

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6
Q

Name some RNA types

A

Coding RNAs

Non coding RNAs loosely divided into 2 classes: Small and long ncRNAs

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7
Q

Name the features of lncRNAs

A

300nt to >100kb in size
mRNA like transcripts
Lack significant open reading frames
Many are transcribed by RNA pol II and are polyadenylated (although exceptions)

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8
Q

What are the two main classes of ncRNAs and their functions?

A

Housekeeping- constitutively expressed and required for normal function and cell viability
Regulatory- expressed only in certain stages of organism development or as a response to external stimuli

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9
Q

What are the features of snoRNAs?

A

60-300nt

Found predominantly in nucleolus

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10
Q

What are the functions of snoRNAs?

A

Act as a guide RNA for post transcriptional modification of rRNAs and some spliceosomal RNAs
Promote alternative splicing through interactions with some protein partners
Functions mediated by formation of duplexes between snoRNAs and RNAs with complementary sequences

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11
Q

Where are snoRNAs encoded?

A

In the introns of protein coding or non-protein coding genes

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12
Q

What can snoRNA loci give rise to?

A

miRNA-like small RNAs

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13
Q

snoRNA pathological significance?

A

Prader-Willi syndrome associated with microdeletion removing a cluster of snoRNAs
U50 snoRNA transcriptionally down-reg in prostate cancer and breast cancer
Non-small cell lung cancer due to amplification of SNORA42

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14
Q

Which snoRNAs are tumour suppressors for which cancers?

A

U50 C/D box snoRNA-breast and prostate cancer
H5sn2 H/ACA snoRNA- Meningioma
RNU43 and RNU44 C/D box snoRNAs- Breast and HNSCC

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15
Q

Major classes of snoRNAs

A

C/D box define target sites for 2’-O-ribose methylation
H/ACA box define target sites for pseudouridylation
scaRNAs variants that mediate alternative splicing in nuclear Cajal bodies

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16
Q

Which snoRNAs can be oncogenes?

A

snoRD33 C/D box
snoRD66 C/D box
snoRD76 C/D box
snoRA42 H/ACA box

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17
Q

What is the RNAi mechanism?

A
  1. dsRNA binds to Dicer
  2. Dicer cleaves dsRNA into smaller fragments (digestion)
  3. One of the RNA strands is loaded into a RISC complex (unwinding)
  4. The complex links to the mRNA strand by basepairing (binding)
  5. mRNA is cleaved and destroyed. No protein can be synthesized (degradation)
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18
Q

What is the significance of RNAi?

A

Defense mechanism against dsRNA-containing viruses
May stabilise the genome by sequestering repetitive sequences such as mobile genetic elements
Control cellular development
Repress protein synthesis and regulate development of organism-miRNAs
Gene silencing

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19
Q

What are the functions of miRNAs?

A

Endogenous triggers of the RNAi pathway
Regulate thousands of human protein-coding genes
Critical roles in tumorgenesis
Regulate developmental processes

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20
Q

What are the differences between RNAi and miRNA translational repression?

A

miRNA are not perfectly complimentary to their targets
miRNAs do not induce target cleavage but block translation by binding to complementary mRNAs
miRNAs encoded by host genome whereas siRNAs in most cases originate from outer source

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21
Q

Which miRNAs are associated with CLL?

A 
Down regulation of
miR-15a 
miR-16-1, 
miR-181a, 
let-7a, 
miR-30d, 
miR-150, 
miR-92
22
Q

Which miRNAs are associated with paediatric Burkitt’s lumphoma, Hodgkin’s lymphoma and diffuse large B cell lymphoma?

A

Up regulation
miR-155,
miR-17-92

23
Q

Which miRNAs are associated with Hodgkin’s disease and Burkitt lymphoma cells?

A

Upregulation
miR-9,
let-7a

24
Q

Which miRNAs are associated with B cell malignancies?

A

Down regulation
miR-143,
miR-145

25
Q

Which miRNAs are associated with AML?

A 
Up regulation
miR-127, 
miR-154, 
miR-299, 
miR-323, 
miR-368, 
miR-370

Downregulation
miR-221,
miR-222

26
Q

Which miRNAs are associated with hematopoietic malignancies?

A

Down regulation

miR-203

27
Q

What are the functions of lncRNAs?

A 
Transcriptional interference
Induce chromatin remodelling and histone modifications
Modulate alternative splicing patterns
Generate endo-siRNAs
Modulate protein activity
Structural or organisational role
Alter protein localisation
Small RNA precursor
28
Q

What is dosage compensation?

A

Equalisating of expression levels from the X chromosome in males and females

29
Q

How is dosage compensation achieved?

A

XIST physically coats one of the two X-chromasomes and is necessary for the cis-activation of over 1000 X-linked genes

30
Q

What regulates XIST and how?

A

Tsix which contains anti-sense sequence of XIST and therefore is able to regulate XIST activity by base-pairing to it

31
Q

How is XIST implicated in human cancer?

A

Expression found to be dysregulated
Inactivated chromosome found to be absent in human cancer specimens
Expression lost in female breast, ovarian and cervical cancer cell lines
Could serve as prognostic marker

32
Q

What is genetic imprinting?

A

A process which results in expression on only one allele of a gene, while the allele originating from the other parent is silenced

33
Q

Why is genetic imprinting important in cancer?

A

It results in altered gene expression

34
Q

What is H19?

A

A locus that encodes a 2.3kb lncRNA that is expressed exclusively from the maternal allele

35
Q

Why is H19 important in human cancer?

A

Loss of imprinting at the H19 locus may result in a variety of cancers (colon, liver, etc)
H19 has both oncogenic and tumor suppression properties
Upregulated in some carcinomas suggesting an oncogenic function for bladder and breast carcinomas

36
Q

What is the relationship between miR-675 and H19?

A

H19 transcripts serve as precursor for miR-675 which is involved in the regulation of developmental genes
miR-675 is processed from the first exon of H19
miR-675b functionally down regulates the tumor suppressor, retinoblastinoma in human colorectal cancer (H19 oncogenic role)

37
Q

What is ANRIL?

A

An antisense transcript to the INK4 locus that spans an estimated region of 30-40kb at chromosome 9p21.

38
Q

What does the INK4 locus encode?

A

Three tumour suppressor genes that are reported to be silenced in prostate cancer

39
Q

Why is ANRIL significant in cancer?

A

It remodels the chromatin landscape and acts as a scaffold molecule by interacting with chromatin modification complexes
Could be initiating factor in cancer formation
Causes abnormal silencing of the INK4 locus

40
Q

What diseases other than cancer are associated with ANRIL?

A

Coronary disease
Intracranial aneurysm
Type 2 diabetes

41
Q

Where is HOTAIR expressed?

A

Developmental HOXC locus located on chromosome 12q13

42
Q

What is the significance of increased HOTAIR expression?

A

It leads to prevention of transcription of several metastasis suppressor genes resulting in metastasis (e.g in breast cancer)

43
Q

What does MALAT-1 regulate?

A

Alternative splicing

44
Q

how does MALAT-1 regulate expression of genes in synapse formation?

A

It is highly abundant in neurons and modulates the activity of neuronal SR splicing factors

45
Q

Which miRNAs can be used as a clinical biomarker for leukaemia?

A

miR-92a and miR-638

46
Q

Which miRNAs can be used as a clinical biomarker for colorectal cancer?

A

Differential expression of miRNA is plasma

47
Q

Which miRNAs can be used as a clinical biomarker for myocardial injury?

48
Q

What are the 2 main therapeutic approaches in which miRNAs are used?

A
  1. miRNA inhbition therapy when the miRNA is over-expressed

2. miRNA replacement therapy when the miRNA is repressed

49
Q

What are AMO’s?

A

Anti-miRNA oligonucleotides that are blocking antisense reagents that inhibit miRNA function by hybridising and repressing the activity of a mature miRNA specific knowckdown of miRNA by ds miRNA mimetics

50
Q

What are AntagomiRs anti-miRs or blockmirs?

A

Chemically engineered AMOS

51
Q

What are miRNA sponges?

A

Engineered ncRNA inhibitors that can be exogenously expressed in cells. Those transcripts contain multiple binding sites to the miRNA of interest and saturate the miRISC complex repressing the activity toward natural mRNA

Advances in Medicine (7 decks)

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