RNA editing Flashcards
what is RNA editing
nucleotide alteration which results in different or additional nucleotide
where does editing occur
mRNA, tRNA and ribosomal RNA (rRNA)
what are the two classes of editing
-insertion/deletion
-modification (e.g A to I)
What is the effect of editing
Change the coding sequence and/or properties of mRNAs
What can be a base modification which produces ‘marked nucleotides’
methylation
Base modification can alter activity, how?
- Additional H bonding potential
- NH2 can be converted to O and therefore have different properties
what are some of the effects of editing on mRNA
- creation of start codon (C->U or U insertion)
- Creation of new open reading frame (nucleotide insertion or changes in AA which effects splice site
- creation of stop codon (U insertion, C->U)
- removal of stop codon (base conversion)
what is the most prevalent internal modification in eukaryotic mRNA
N6-methyladenosine
How is conversion to N6-methyladenosine regulated
Writers - Mettl3
Readers - Hu-R
Erasers - FTP
what are methyltransferases function
stem cell differentiation, circadian rhythm, cell cycle, splicing and more
what is (I_) recognised as guanosine
Inosine
What is produced by enzymatic deamination during RNA editing
Inosine (from adenosine)
Uracil (from cytosine)
what is the effect of mRNA editing in relation to ApoB
- Intestine there is editing so C->U
- Liver there is no editing
- no editing means that LDL-receptor binding section is translated producing ApoB-100
What is the type of editing of ApoB-48
Cytidine deamination
what carries out ApoB editing?
APOBEC-1 found in intestine which is linked to cholesterol control, cancer development and inhibition of viral replication
What is the difference between Apo-B-48 and ApoB-100
ApoB-100 has an LDL-receptor binding domain whihc is linked to atherosclerosis
what is the difference between Q and R site of glutamate receptor
Q- allows transport of both Na+ and Ca2+
R- only transport of Na+
What is the editing involved in the differentiation of Q/R sites
adenosine deaminase by ADAR2
what is the effects of mutations in mouse ADAR2 gene
lead to seizures, post-natal death, neurodegeneration in the hippocampus
What is a modification of ribose
2’-O methylation
what are the RNAs which contains 2’-O-methylation
tRNA, rRNA and snRNA
what are the effects of modification of rRNA
- Yeast doesn’t survive without 2’-0-methylation in ribosomal RNA
- Removal of Y from yeast leads to defects in translation
what is mutated in dyskeratosis congenita
Human Y synthase
How is tNRA transported through the nuclear pore
In conjugation with Exp-t and Ran GTP
How is miNRA transported through the nuclear pore
How is tRNA transported through the nuclear pore
In conjugation with Exp-t and Ran GTP
How is miRNA transported through the nuclear pore
With Exp-5 + Ran GTP
How is snRNA transported through the nuclear pore
CRMI with Ran GTP as well CBC+PHAX
How is mRNA transported through the nuclear pore
Tap/Mex67 +p15/Mtr2 as well as CBC+ALY/Yral
How is rRNA transported through the nuclear pore
in a vesicle, CRM1+Arxl+Mex67+Mtr2 as well as Nmd3 with RAN GTP
why is mRNA localise
-localised protein synthesis
-Generate cell polarity
-prevents expression in the wrong place
- promotes efficiency of subsequent protein targeting
-local control of translation
why is local control of translation important
synapses
why is efficiency of subsequent protein targeting important
ß-actin in fibroblasts
what are the two methods of localisation
Diffusion based
Active transport based
how does diffusion based location work
free movement + local entrapment
how does active transport based localisation work
- Nuclear processing then export
- RNP remodelling
- RNP transport using cytoskeleton as vehicle
- Anchoring then translation