lecture 8 Flashcards
RNA editing
nucleotide alterations which result in different or additional nucleotides in the mature RNA
RNA editing occurs in the 3 major classes of RNA
mRNA, tRNA, ribosomal RNA
two classes of editing
insertion/deletion
modification (e.g. A to I, C to U, U to C)
base modification
eg methylation
this is reversible
can change chemical properties of the base
base modification
altered identity
flip purines (A to I (same as G))
ands flip pyrimidines (C to U)
via deamination
effect of mRNA editing
eg
can create start and stop codons by inserting a U
(AUG - start)
can have a C and convert to a U
can change slice sites
N6 - methyladenosine
methyl group added to an A (m6A)
regulated by writers (add methyl group), readers (recognise) and erasers (remove methyl group)
writer example
Mettl3
reader example
Hu-R, YTHDF1-3
eraser example
FTP, AKLBH5
what does it cause
hydrogen bond to U doesnt change
affects protein binding - sometimes reader protein only recognises the mRNA when its methylated or sometimes m6A blocks the reader protein
m6A can make mRNA more stable which increases mRNA content and protein production or
it may cause a target for degradation of the mRNA so the mRNA level is decreased
depends on the mRNA and the protein it recruits as to the impact
RNA editing by deamination (change one base for another)
cytosine deaminated is
uracil
adenosine deaminated is
inosine (recognised as guanine)
UAA is a common stop codon
is you change the C is CAA to a U you have a
stop codon
creates a smaller protein
in the liver there is
no editing
for example in the liver a protein called ApoB-100 is made (full length) contains an LDL-receptor binding site, in the intestine we have
editing so the protein so CAA is changed to UAA shorter protein ApoB-48 is made, this has no LDL-receptor binding. editing is carried out by the APOBEC-1 enzyme
A to I change
edit in the Q/R site of the glutamate receptors
Q is changed to R after editing
occurs in L-glutamate major excitatory neurotransmitter
it normally lets sodium and calcium through
editing decreases the calcium permeability of the channels
signalling is reduced
editing carried out by ADAR2 gene
RNA modification - ribose
methylation of 2 ribose from a OH group (2-0-methylation)
changes property of ribose
methylation stabilises 5’ end of DNA
the nuclear pore
on nucleoplasmic side theres a cage structure
on cytoplasm site theres filaments
RNA is an acid meaning its charged and the pore is hydrophobic meaning RNA wont go through on its own
tRNA export factor is
Exp-t
miRNA (micro RNA) export factor is
Exp-5
snRNA binds to cap binding complex (CBC) and has an export factor called
PHAX which binds CRM1 which exports proteins
mRNA binds to CBC and ALY/Yra1 which binds to export proteins
TAP/Mex67 and p15/Mtr2
rRNA is large so has lots of export adapters and export proteins
why localise mRNA
localised protein synthesis
prevents expression in the wrong place
diffusion based-localisation
protein bound to mRNA binds to anchor proteins at the site you want them to be so mRNA diffuses with the them
