RNA editing Flashcards
What are the consequence of RNA editing on RNA?
- Editing in non-coding regulates RNA maturation/expression at different levels
- Editing within coding sequences generates different/novel protein isoforms
Explain apoB gene editing.
- aboB mRNA in the liver is translated into apoB-100 protein
- aboB mRNA in the intestine is editied by APOBEC1 such as the CAA codon is made into a UAA codon. As a result, intestinal cells produce aboB-48 which corresponds to the N-terminal domain of aboB-100
What is APOBEC1?
Member of the APOBEC family of proteins that are involved in RNA editing. It acts on ssRNA, contains a ZDD domain that carries out deamination.
It binds to ACF that recognizes specific RNA sequences as APOBEC1 does not have high affinity for ssRNA.
What is ADAR?
Adenosine deaminases acting on RNA. Bind dsRNA and edits A to I.
What is a unique characteristic of ADAR2 and when is this mechanism used?
ADAR2 edits its own RNA. This occurs when there is too much ADAR2. It will edit its own RNA such as to introduce an alternative splicing site. The resulting RNA is 47 nucleotides longer than usual, but since 47 is not a multiple of 3, it produces nonproductive RNA.
What is the main target of ADAR?
Non-coding regions such as Alu sequences in introns
How does ADAR1 prevent innate immune response to dsRNA mediated by MDA5?
ADAR1 edits dsRNA by converting A to I. The presence of I in dsRNA inhibiits MDA5 activation, preventing anti-viral immune response to self dsRNA
Give a biological example where A-to-I editing is present in common.
GlutR-B is a subunit of glutamate receptor that is edited by ADAR2 that switches glutamine to arginine. Nearly all Glut-B is edited in the brain.
What happens in the absence of ADAR2 in the brain in mice?
Epileptic seizures. ADAR2 switches glutamine to arginine. Arginine has a positive charge such as modified GlutR-B can reduce Ca2+ influx. If this influx is not reduced, it causes seizures.
