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RNAi is antagonized by A-->I hyper-editing
1Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
EMBO Reports
|December 18, 2001
Summary
Adenosine to inosine conversion by ADAR2 inhibits RNA interference (RNAi). Increased deamination of double-stranded RNA (dsRNA) progressively blocks siRNA production, explaining RNAi inhibition.
Area of Science:
- Molecular Biology
- Virology
- Biochemistry
Background:
- RNA interference (RNAi) and adenosine to inosine (A-to-I) conversion are dsRNA-responsive pathways with potential antiviral functions.
- RNAi degrades mRNA via siRNAs, while A-to-I editing alters RNA coding and structure.
Purpose of the Study:
- To investigate the impact of A-to-I RNA editing on the RNAi pathway.
- To determine if ADAR2-mediated deamination affects dsRNA processing into siRNAs.
Main Methods:
- Treatment of dsRNA with ADAR2 enzyme to induce A-to-I editing.
- Analysis of siRNA production and RNAi efficiency in response to edited dsRNA.
Main Results:
- ADAR2-mediated deamination of dsRNA inhibits RNA interference.
- Progressive inhibition of RNAi correlates with increased levels of dsRNA deamination.
- dsRNA hyper-editing is sufficient to explain the observed inhibition of RNAi.
Conclusions:
- A-to-I RNA editing by ADAR2 antagonizes the RNAi pathway.
- This interaction suggests a regulatory mechanism where RNA editing can suppress RNAi-mediated antiviral defense.
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