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Path 19.01 and 19.07 > 20.1.10 Functional Noncoding RNAs > Flashcards

20.1.10 Functional Noncoding RNAs Flashcards

1
Q

Give 4 examples of functional non coding RNAs

A
  • Ribosomal RNA (rRNA)
  • Small nuclear (snRNA)
  • Small nucleolar RNA (SnoRNAs)
  • Transfer RNA (tRNA)
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2
Q

How many rRNA molcules are there

A
  • 5 molcules

- 5S, 28S, 5.8S, 16S, 23S

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3
Q

What are cytoplasmic ribsosomes composed of

A
  • Large 60S ribosomal unit associated with 28S, 5.8S and 5S rRNA
  • Small 40S subunit associated with 18S rRNA.
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4
Q

What are mitochondrial ribsosomes composed of

A
  • 16S rRNA associated with small mitochondrial ribosomal subunit and
  • 23S rRNA associated with the large mitochondrial subunit.
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5
Q

Where is rRNA synthesised and where does biogenesis of ribosomes take place

A

Nucleolus

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6
Q

Which rRNAs are encoded by a 13kb multigenic transcription unit

A

-18S, 5.8S, 28S

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7
Q

Where is the 13kb multigenic transcription unit encoding 18S, 5.8S and 28S found

A

-On the short arms of acrocentric chromosomes (13, 14, 15, 21, 22)

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8
Q

Which rRNAs are cleaved from H strand of mtDNA?

A

23S and 16S

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9
Q

What are ribosomopathies

A

-Heterogeneous group of disorders that result from ribosome dysfunction.

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10
Q

What is the disease mechanism in ribosomopathies

A
  • Disrupted ribosome biogenesis leads to accumulation of free ribosomal proteins that bind the p53 suppressor MDM2, leading to activation of p53. This then causes increased apoptosis and cell death.
  • or. Ribosomes from different tissues may have different compositions, which is critical to the translation of specific mRNAs.
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11
Q

Examples of mutations in ribosomal proteins

A
  • 5q minus syndrome (myelodysplastic syndrome) is due to haploinsufficiency of the RP514 gene.
  • Diamond Blackfan anemia is an inheited bone marrow failure syndrome. Cuased by haploinsufficiency of the gene encoding RPS19.
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12
Q

Examples of defects in ribosome biogenesis

A
  • Treacher Collins syndrome is caused by AD mutations in TCOF1 or POLR1D or AR mutations in POLR1C/D. All expressed in neural crest cells and encode proteins involved in ribogenesis
  • Shwachman Diamond syndrome is characterised by bone marrow failure, risk of MDS, AML. Caused by AR mutations in SBDS gene Leads to impaired maturation of large ribosomal subunit.
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13
Q

What are spliceosomal small nuclear RNAs (snRNA)

A
  • 106-186 nucleotides long and required for functioning of the two spliceosomes
  • 9 human snRNAs
  • Uradine rich
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14
Q

What else is a spliceosome composed of

A
  • snRNAs
  • snRNPs (small nuclear ribonucleo proteins)
  • non-snRNPs
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15
Q

What are the two types of spliceosome

A
  • Major U2- dependent

- Minor u12-dependent

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16
Q

What is the major spliceosome composed of

A

snRNAs U1, U2, U4, U5, U6.

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17
Q

What does the major spliceosome target

A

CU-AG introns in pre-mRNA splicing

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18
Q

What is the minor spliceosome composed of

A

U4atac, U6atac, U11, U12

19
Q

What does the minor spliceosome target

A

Rare AU-AC introns.

20
Q

What are the two subclasses of spliceosomal snRNAs

A
  • Sm-class

- Lsm-class

21
Q

What do sm class of snRNAs have

A
  • They have a consensus Sm site, directs the assembly of a ring of 7 Sm core proteins.
  • e.g. U1, U2, U4, U4atac, U5, U7, U11, U12
22
Q

What do Lsm-class of snRNAs have

A

Terminating stretch of uradines (Lsm site) that form the binding site for a ring of 7 Lsm core proteins.

23
Q

Examples of non-spliceosomal snRNAs

A

U1 and U2

24
Q

What function does U1 have

A

-Stimulates transcription by RNA Pol II

25
Q

What function does U2 have

A

-Stimulates transcription elongation by RNA Pol II

26
Q

Spliceosomes and disease. What autosomal recessive disorder is caused by mutations in RNU4ATAC

A
  • Microcepahlic osteodysplastic primordial dwarfism type 1 (MOPD1).
  • Mutations alter secondary structure of snRNA
27
Q

How is spinal muscular atrophy linked to snRNAs

A
  • SMN2 is needed for paturation of snRNPs.
  • SMN2 mutations lead to haploinsufficiency, causing a decifit in snRNP assembly capacity.
  • Consequently leads to spinal motor neuron death
28
Q

How is retinitis pigmentosa linked to snRNAs

A
  • Autosomal dominant
  • 5% cases due to mutations in genes encoding protein components of snRNP complexes (PRPF31, PRPF8, HPRP3, PAP1, SNRNP200).
  • Mutations lead to death of retinal photoreceptor cells.
29
Q

What are small nucleolar RNA (snoRNA)

A

RNAs (60-300nt long) that have a function in RNA modification and processing

30
Q

What two classes of snoRNAs are there

A
  • C/D box
  • H/ACA box
  • Based on their conserved secondary structures and associated modification reactions.
31
Q

What do C/D box snoRNAs do

A

-Sequence specific 2’-O-methylation fo rRNAs, snRNAs and tRNAs

32
Q

What do H/ACA box snoRNAs do

A

Pseudouridylation of rRNA to generate a mature product.

33
Q

What transcribes snoRNAS

A

RNA Pol II

34
Q

Are snoRNAs ubiquitously expressed

A

Yes (mostly, some are tissue specific)

35
Q

How is Prader-Willi syndrome linked to snoRNAs.

A

PWS is caused by loss of expression of C/D box snoRNAs encoded within paternally expressed SNRPN locus

36
Q

What are transfer RNAs (tRNAs)

A
  • 75-95 nts.

- Transfer the correct amino acid to the ribosome during protein synthesis

37
Q

Where are tRNAs encoded

A

Nuclear and mitocondrial DNA

38
Q

What structure do tRNAs have

A
  • Clover leaf
  • 3 hairpin loops: anticodon loop (3 nucleotides that base pair with mRNA), D-loop and T-loop
  • Mitochondrial tRNAs have a non-classical structure and a decreased melting temperature
39
Q

What chemical modifications do tRNAs get after synthesis

A

pseudouridine and dihydrouridine

40
Q

What synthesises tRNAs

A

RNA Pol III

41
Q

What is wobble base pairing (tRNAs)

A

-Third base of tRNA anticodon can form a hydrogen bond with more than one type of base at the 3’ position of a codon

42
Q

Name two diseases caused by mutations in mitochondrial tRNAs

A
  • MELAS (mitochondrial encephalopathy, lactic acidosis, stroke-like episodes)
  • MERRF (myoclonic epilepsy with raged red fibers).
  • Both conditions are associated with the failure to modify tRNAs with taurine.
43
Q

What causes MELAs

A
  • MELAS (mitochondrial encephalopathy, lactic acidosis, stroke-like episodes)
  • MTTL1 gene mutations (mt-tRNALeu gene).
  • Causes a complex 1 deficiency
44
Q

What causes MERRF

A
  • MERRF (myoclonic epilepsy with raged red fibers).

- m.8344A>G mutation in mt-tRNALys gene

Path 19.01 and 19.07 (45 decks)

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