RR13 Flashcards
What are the important mechanisms in RNA quality control?
1) SR proteins: define exons so introns can be appropriately excised
2) Polyadenylation of pre-mRNA
3) Export factors are loaded onto mRNA
4) Remaining factors must be removed in pioneering round of translation
If the important mechanism in RNA quality control do not work, or there are other issues, what process takes place?
There is nonsense mediated decay. There are nuclear proteins bound to exons, they make their way through pore, pioneering round is critical, as ribosomes travel through tRNA, they knock off any proteins associated with mRNA.
- Process of mRNA surveillance to ensure these are eliminated
What happens if a truncate protein is lacking major functional domains?
This functional domains could be essential genes, so if it is lacking this is dangerous. It is normally recognized at pioneering round of translation.
Stability of mRNA has a very high ___
Variance (life length)
What do short-lived mRNAs in eukaryotes contain?
They contain AUUA in their 3’ UTR.
Addition of these sequences often destabilize mRNA, they are repetitive elements, and lead to a lower variance (shorter life length)
How does RNA decay work?
- RNA decay can occur at both ends of RNA
- Sometimes it could be cleaved in the middle, then degraded by both exonucleolytic pathways
- It works by exosome which is a complex that works by degrading mRNA before carrying out its actual function which is deadenylation of a polyA tail
- 3 - 5’ decay
- Degradation at 5’ ends - decapping
- XRNI 5’ -> 3’ decay
- RNA is threaded through a structure, exonuclease activity takes place on one send, endo on the other end
What is TFR?
It is a mammalian transferrin receptor. It regulates in response to iron concentration. It has stem loops in untranslated regions.
It is an Iron response element binding protein and it can be active or inactive.
What form do you want TFR to be if you have high iron vs low iron?
- If you have high iron, you want it to be inactive. TFR mRNA is degrading and unstable.
- In low iron, TRE takes on an active conformation.
What is the function of IREBP active?
It protects mRNA and blocks proteins recruiting in machinery.
What does mRNA abundance reflect?
It reflects the protein levels. more mRNA = more protein.
If there is a skew in the relationship between mRNA and protein levels, what could this reflect? What is an example of this?
It may indicate that protein synthesis or stability is regulated.
Example: Inhibition of mRNA translation impacts drosophila development.
Has a uniform mRNA distribution, but the hunchback protein has a very steep anterior to protesrior gradient. 2 genes hunchback at anterior, 1 nanos at prosterior (specify these regions)
In nanos, there is a protein made here, that shows mRNA not linked to protein levels without nanos, protein is made everywhere in the embryo, which is lethal for the larva. Nanos ensures hunchback is only translated antierior.
How can the stability of some RNAs be regulated?
1) Ferritin (protein), binds iron ions, preventing the accumulation of toxic iron.
2) In low iron systems, IRE-BP binds to 5’ UTR of ferritin, inhibiting translation. -> don’t need ferritin.
What is a defect in C-elegans and what is the sequence that could correct this defect?
- The defect is that the c-elegans never leaves its larval stage (Lin4)
This allows understanding of timing of events.
But they found a sequence that could correct this defect.
lin-14 codes first stage, variant does not have 3’ UTR, it is important for lin14 to go away so we can get to next stage.
lin4 encoded phenotype, an RNA lin4 which is a lin14 base paired along with UTR.
lin4 blocks translation of lin14. lin14 is constantl made.
