4- Mrna Processing Flashcards
What are the splice donor and acceptor site
Donor: 5’ end of gene (GU)
Acceptor: 3’ end of gene (AG)
Which end of the gene is the promotor
5’
What is a lariat intermediate
By product of RNA splicing
What happens to pre- mRNA to become mRNA
Theadditionof a 5’CAPmolecule to the 5’ end
o Theadditionofa poly A tail to the 3’ end
o Theremovalofintronsviasplicing
What is the general intron sequence
GU—————-Pyr15NCAG,
What is the sequence of snRNP binding
U1 to donor site, U2,4,6 then U5 to acceptor site
How is the lariat structure formed
The GU loops back to an A residue in the intron
The G forms a phosphodiester bond with this A residue between the 5’ phosphate group on the G and the 2’ OH on the G
This causes the splice acceptor site to be cleaved, the end of the intron is removed from the next exon, and the intron is removed as a lariat structure
What is the function of the 5’ cap
protect mRNA at the 5’ end and also greatly enhances the translation of mRNA
How is the 5’ cap formed
hydrolysis of the triphosphate on the end of the 5’ of the mRNA to a diphosphate
This reacts with the α phosphate of a GTP to
form a 5’ 5’ phosphate linkage
The cap is further modified at the N7 position in the purine ring to form a 7 methylguanylate cap
(done by methyl transferase)
How is the poly A tail formed
poly A polymerase (PAP) adds, one at a time, approximately 200 A nucleotides to the end of the mRNA sequence
How significant are mutations in RNA processing in heritable disease
~13%ofcasesfeaturemutationsingenepromoters
o ~6%ofcasesfeaturemutationsofthepoly Asequence
o ~1.2%featuremutationsofRNAcapping
o ~33%featuremutationsinthesplicedonor/acceptorsequences
Remaining due to faulty proteins after translation
What is thalassaemia
Inherited disorder with imbalance of alpha and beta Hb chains, so Hb not functional. Some types due to mutated splice sites
What are some symptoms of thalassaemia
severe anaemia, extramedullary haematopoiesis, hepatomegaly, hepatospenomegaly
Iron overload (haemosiderosis) – elevated GI absorption of iron due to chronic anaemia: hepatic fibrosis, darkening of skin, cardiomyopathy, endocrinophaties i.e. diabetes etc.
What is polio
Polio causes poliomyelitis, which invades the nervous system, causing total paralysis in a matter of
hours
It does this by making an enzyme that cleaves the 5’ cap, replacing it with its own. Thus, they are
no longer a template for translation. Viral proteins are produced instead
What is DMD
Mutations in the dystrophin gene causes muscle wastage with age
