RNA biology lecture 6 Flashcards
1
Q
Cap snatching by influenza
A
- Capping confers stability + ensures export from nucleus
- Depends on RNAPII
- Creates issue for virus which transcribe host DNA w/ own polymerase as lack CTD
- RNA virus often replicate in cytoplasm, use cells capping machinery
- Influenza virus = in nucleus, x have CTD, steals cap form emerging pre-mRNA w/ endoribonuc acclivity
- Cap is used as a primer to initiate transcription of its own RNA
- Viral RNA then capped so protected from 5’-3’ degradation + exported to cytoplasm
- Host RNA x have cap, vulnerable to nucleases
2
Q
Capping, early checkpoint release + disease
A
- Protein encoded by herpes simplex virus inhibits action of CDK9, prevents phosph of Ser 2
- Pol stalls at early checkpoint + x released, host transcripts suppressed
3
Q
Mutations that affect pre-mRNA processing
A
- Mutations often found in regions needed for processing machinery to assoc w/ pre-mRNA e.g. 5’SS, ESE, 3’SS
- Mutation affecting splice site → ↓ splicing of exons + faulty mRNA
- Mutation in polyA signal ↓ or ↑ cleavage + poly adenyl
- 2 types of mutation: 1. splicing mutation that directly effect consensus signal cause exon skipping, 2. mutation that affect trans-factor so impair splicing machinery
- E.g. fontrotemporal dementia has mutations in MAPT genes
E,g, Tau enriched in axons, Tau3/4 ration is highly regulated, deviation → accumulation of Tau → neuroses. - E.g. DMD caused by deletions + mutations e.g. T→A sub in exon 31 that creates an ESS forces exon31 skipping
- Mutation in cis-elements: can promote cancer initiation + progression e.g. KIT oncogene
- Mutation in splicing factors:
- E.g. PWS = ↑ symptoms like restricted growth
- Deletion of paternal SNURF-SnRNP causes PWS by loss of snoRNA, SnoRNA HB11=S2 comp to 5HT2CR pre-mRNA
- PWS = mutation in 5HT2CR, deletion in chromosome 15 that encodes snoRNA inc SNORD115
- SNORD115 assoc w/ exon 5 + suppresses activation of 5a splice site
4
Q
Mis-splicing in cancer
A
- No. of mutations that inactivate splice sites either directly or indirectly by affecting splice regulatory sequencing
- Mutations to spliceosome e.g. U2AF
5
Q
3’ end formation + disease
A
- Largely occur in essential cis-elements, leads to Low or Gof
- E.g. thalassemia due to mutation in AATAAA hexamer (recognition signal needed for interaction of CPSF w/ pre-mRNA)
- Mutation in B globin gene Δ hexamer so CPSF x recognise → ↓ B globin protein → aggregation
- Mutation in coagulation factor III where weak consensus site
6
Q
Influenza A virus
A
- Virus transcribes template, poly-adenyl occurs by transcribing U-rich region in template strand + repeatedly copying U-stretch → export
- mRNA translated to make NS1 which assoc. w/ CPSF1
- AAUAAA in pre-mRNA comprises host mRNA
- NS1 also inhibits splicing by binding + inactivating u6 snRNP