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Stem-loop structure preference for site-specific RNA editing by APOBEC3A and APOBEC3G
Shraddha Sharma1, Bora E Baysal1
1Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, United States of America.
Peerj
|December 13, 2017
Summary
APOBEC3A and APOBEC3G enzymes perform C-to-U RNA editing. They preferentially edit RNA substrates with specific stem-loop structures, influenced by loop size and stem stability.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- APOBEC3A (A3A) and APOBEC3G (A3G) are cytidine deaminases with known antiviral and anti-retrotransposon functions.
- These enzymes possess a novel C-to-U RNA editing capability.
- While they deaminate DNA at multiple TC/CC sites, their RNA editing is more restricted, often targeting single TC/CC sites.
Purpose of the Study:
- To investigate the specific sequence and structural preferences of APOBEC3A and APOBEC3G for RNA editing.
- To elucidate the factors governing substrate and site-specificity in A3A and A3G-mediated RNA editing.
Main Methods:
- Site-directed mutagenesis of endogenous cellular RNA substrates.
- Analysis of RNA editing levels in response to sequence and structural modifications.
Main Results:
- Both APOBEC3A and APOBEC3G exhibit a preference for RNA substrates featuring a predicted stem-loop structure.
- The target cytosine is preferably located at the 3'-end of the RNA loop.
- RNA editing efficiency is significantly impacted by loop size, nucleotides adjacent to the target cytosine, and stem stability.
Conclusions:
- RNA editing by APOBEC3A and APOBEC3G is dictated by both RNA sequence and secondary structure.
- These findings provide a mechanistic explanation for the observed substrate and site-specificity of A3A and A3G RNA editing.