Rna degradation/turnover Flashcards
Why is rna degraded sometimes
Damaged mrna Eg incorrect editing
Or to control gene expression levels
What can mrna half life be increased by (reduced turnover/degradation)
Stability Eg via poly A tail, 3’ utr
For degradation. What needs to happen to mrna
De circularisation by removing either cap or poly a tail
What 3 enzymes are involved in phase 1 degradation
Decapping enzymes (eg dcp 1 or 2)
Endonucleases
Deadenylases
Give an example of an endonuclease in phase 1 degradation
Argonaute
What is the most famous deadenylase
Ccr/not
Do both cap and poly a need removed for degradation
No. One or the other is fine for exonucleases activity
How do endonucleases like argonaute work
They cleave rna in the middle which means either cap or poly a is attached. Allows degradation
Which exonucleases 5’ to 3’ functions after decapping
XRN1
What is XRN1 for
Rna turnover and processing
Also involved in txn termination early (5’ end)
What is the diff between turnover and processing
Processing is just degradation of a part of rna
Which complex has 3’ to 5’ exonuclease working after deadenylation
Exo some complex
What are the 2 3’ to 5’ exonulceases in the exosome complex
Rrp6 and 44
What is deadenylation dependant decay
Overtime there is gradual loss of poly A via deadenylases like ccr not
This can cause degradation via exosome activity rrp6 and 44
What 4 things trigger deadenylation dependant decay via ccr not
AU rich sequences (AREs)
Nonsense codons (PTCs)
C fos coding sequences
Mirna
Deadenylation independent decay is endonuclease activity (argonaute) or what else
Auto regulation of own mrna translation levels
Give an example of auto deadenylation regulation independent decay
RPS 28B ribosome protein recruits edc3 decapping protein to recap it’s own mrna for degration
What is degradation due to nonsense codons called
Nonsense mediated decay nmd
What are premature stop codons PTCs due to
Errors in txn, splicing, editing, polyadenylation or mutations
Stop codons are usually in final exons. What constitutes a target for nmd
A ptc which is above 55 nucleotides from the last exon junction
What bind close to exon junctions which get cleaved by ribosomes
Exon junction complexes EJCs
If a ptc occurs 55 above nucleotides before a last exon junction what happens
Ejc will stay there as ribosome will stop prematurely so can’t cleave it
This ejc will attract UPF proteins which causes rna degradation
What is process of nmd called
Surveillance
Out of siRna and mirna. Which one makes a perfect complimentary binding to mrna
SiRna
are si rna and mi rna diff in size
No. Both 21-23 nucleotides long
Which out of si rna and mi rna is a viral defence mechanism (get it from ds viral rna)
Si rna
How does si rna degrade rna from virus
The ds rna from virus is cleaved and unwound by dicer
1 strand binds with the risc complex which has endonucleases like argonaute
Cleaves in the middle of mrna allowing degradation (independent decay)
What is mi rna for
Blocking translation and further degradation
How is mirna made
Mirna gene is processed by drosha enzyme
Then exported out by exportin 5
Cleaved and unwound by dicer
Binds with risc complex
Binds to the 3’ utr stopping translation and causing degradation
Are longer utrs or short utrs required for mirna blocking translation
Longer utrs (usually in slowly growing cells)
Why is it good fast growing proliferating cells have short utrs
Less mirna binding sites. They can’t block translation because they need proteins for growth
What can si rnas be used for
Research into knock down genes
