20.1.10 Functional Noncoding RNAs Flashcards
Give 4 examples of functional non coding RNAs
- Ribosomal RNA (rRNA)
- Small nuclear (snRNA)
- Small nucleolar RNA (SnoRNAs)
- Transfer RNA (tRNA)
How many rRNA molcules are there
- 5 molcules
- 5S, 28S, 5.8S, 16S, 23S
What are cytoplasmic ribsosomes composed of
- Large 60S ribosomal unit associated with 28S, 5.8S and 5S rRNA
- Small 40S subunit associated with 18S rRNA.
What are mitochondrial ribsosomes composed of
- 16S rRNA associated with small mitochondrial ribosomal subunit and
- 23S rRNA associated with the large mitochondrial subunit.
Where is rRNA synthesised and where does biogenesis of ribosomes take place
Nucleolus
Which rRNAs are encoded by a 13kb multigenic transcription unit
-18S, 5.8S, 28S
Where is the 13kb multigenic transcription unit encoding 18S, 5.8S and 28S found
-On the short arms of acrocentric chromosomes (13, 14, 15, 21, 22)
Which rRNAs are cleaved from H strand of mtDNA?
23S and 16S
What are ribosomopathies
-Heterogeneous group of disorders that result from ribosome dysfunction.
What is the disease mechanism in ribosomopathies
- 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.
Examples of mutations in ribosomal proteins
- 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.
Examples of defects in ribosome biogenesis
- 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.
What are spliceosomal small nuclear RNAs (snRNA)
- 106-186 nucleotides long and required for functioning of the two spliceosomes
- 9 human snRNAs
- Uradine rich
What else is a spliceosome composed of
- snRNAs
- snRNPs (small nuclear ribonucleo proteins)
- non-snRNPs
What are the two types of spliceosome
- Major U2- dependent
- Minor u12-dependent
What is the major spliceosome composed of
snRNAs U1, U2, U4, U5, U6.
What does the major spliceosome target
CU-AG introns in pre-mRNA splicing
What is the minor spliceosome composed of
U4atac, U6atac, U11, U12
What does the minor spliceosome target
Rare AU-AC introns.
What are the two subclasses of spliceosomal snRNAs
- Sm-class
- Lsm-class
What do sm class of snRNAs have
- 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
What do Lsm-class of snRNAs have
Terminating stretch of uradines (Lsm site) that form the binding site for a ring of 7 Lsm core proteins.
Examples of non-spliceosomal snRNAs
U1 and U2
What function does U1 have
-Stimulates transcription by RNA Pol II
What function does U2 have
-Stimulates transcription elongation by RNA Pol II
Spliceosomes and disease. What autosomal recessive disorder is caused by mutations in RNU4ATAC
- Microcepahlic osteodysplastic primordial dwarfism type 1 (MOPD1).
- Mutations alter secondary structure of snRNA
How is spinal muscular atrophy linked to snRNAs
- 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
How is retinitis pigmentosa linked to snRNAs
- 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.
What are small nucleolar RNA (snoRNA)
RNAs (60-300nt long) that have a function in RNA modification and processing
What two classes of snoRNAs are there
- C/D box
- H/ACA box
- Based on their conserved secondary structures and associated modification reactions.
What do C/D box snoRNAs do
-Sequence specific 2’-O-methylation fo rRNAs, snRNAs and tRNAs
What do H/ACA box snoRNAs do
Pseudouridylation of rRNA to generate a mature product.
What transcribes snoRNAS
RNA Pol II
Are snoRNAs ubiquitously expressed
Yes (mostly, some are tissue specific)
How is Prader-Willi syndrome linked to snoRNAs.
PWS is caused by loss of expression of C/D box snoRNAs encoded within paternally expressed SNRPN locus
What are transfer RNAs (tRNAs)
- 75-95 nts.
- Transfer the correct amino acid to the ribosome during protein synthesis
Where are tRNAs encoded
Nuclear and mitocondrial DNA
What structure do tRNAs have
- 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
What chemical modifications do tRNAs get after synthesis
pseudouridine and dihydrouridine
What synthesises tRNAs
RNA Pol III
What is wobble base pairing (tRNAs)
-Third base of tRNA anticodon can form a hydrogen bond with more than one type of base at the 3’ position of a codon
Name two diseases caused by mutations in mitochondrial tRNAs
- 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.
What causes MELAs
- MELAS (mitochondrial encephalopathy, lactic acidosis, stroke-like episodes)
- MTTL1 gene mutations (mt-tRNALeu gene).
- Causes a complex 1 deficiency
What causes MERRF
- MERRF (myoclonic epilepsy with raged red fibers).
- m.8344A>G mutation in mt-tRNALys gene
