lecture 10 Flashcards
Why is RNA degraded?
Damaged mRNA, incorrectly transcribed/processed mRNA, control gene expression
How does casein mRNA show an increase of half-life in the presence of pro-lactin?
mRNA increase ~70 fold on stimulation by pro-lactin (hormone promoting milk production)
BUT transcription only increase ~2 fold
Half-life increases ~40 fold in response to pro-lactin
PolyA tail length increases
3’ UTR of RNA binds proteins which aid stabilisation
Why is mRNA circular during translation?
monitors mRNA integrity - won’t be circular if it has lost cap or polyA
brings ribosomes ending translation close to the AUG (ribosomes may recycle onto 5’ end)
What is phase 1 of mRNA degradation?
Decapping enzymes - DCP1, DCP2
Endonucleases - Argonaute, Swt1, Smg6
Deadenylases - Ccr/Not complex
These enzymes initiate the breakdown of the RNA
What is phase 2 of mRNA degradation?
5’ to 3’ exonucleas - XRN1
3’ to 5’ exonuclease - the exosome
What is the exosome?
The main 3’ to 5’ exonuclease in the cell involved in RNA turnover and processing
Multisubunit complex
Multiple nuclease activities - RRP6, RRP44
The rest of the subunit function is RNA binding and unwinding
What is XRN1?
5’ to 3’ exonuclease involved in RNA turnover, RNA processing and transcription termination
Functions after decapping of the mRNA
What is deadenylation-dependent decay?
-mRNA is transported to cytoplasm
-polyA tails undergo shortening at different rates to 10-60 nucleotides
-decreases translatability
What happens in deadenylation-dependent decay?
A mechanism whereby all mRNAs gradually lose their polyA tails
What is deadenylation-independent decay?
Autoregulation (negative feedback) - Rps28B binds its own message
Edc3 is one of several activator of decapping enzymes in the cell
Nucleases targetig specific substrates
What is nonsense mediated decay?
Mistakes in RNA are detected, RNA is targeted for degradation
Premature stops codons (PTCs) result from errors in: transcription, splicing, editing, polyadenylation, mutations
How many inherited disorders are caused by nonsense or frameshift mutations that introduce PTCs?
1/3
What is the mechanism for nonsense mediated decay?
exon junction complexes (EJC) are removed from the mRNA by the ribosome
When ribosomes reach the premature stop codons (PTC), an EJC remains downstream - specific factors (UPF proteins) that are part of the EJC are recruited to interact with the RNA degradation machinery
What needs to happen to mRNA before the cap and polyA tail are removed?
it needs to be de-circularised
What does RNAi stand for?
RNA interference
