Stem-loop structure preference for site-specific RNA editing by APOBEC3A and APOBEC3G
APOBEC3A and APOBEC3G cytidine deaminases inhibit viruses and endogenous retrotransposons. We recently demonstrated the novel cellular C-to-U RNA editing function of APOBEC3A and APOBEC3G. Both enzymes deaminate single-stranded DNAs at multiple TC or CC nucleotide sequences, but edit only a select set of RNAs, often at a single TC or CC nucleotide sequence. To examine the specific site preference for APOBEC3A and -3G-mediated RNA editing, we performed mutagenesis studies of the endogenous cellular RNA substrates of both proteins. We demonstrate that both enzymes prefer RNA substrates that have a predicted stem-loop with the reactive C at the 3′-end of the loop. The size of the loop, the nucleotides immediately 5′ to the target cytosine and stability of the stem have a major impact on the level of RNA editing. Our findings show that both sequence and secondary structure are preferred for RNA editing by APOBEC3A and -3G, and suggest an explanation for substrate and site-specificity of RNA editing by APOBEC3A and -3G enzymes.
[…] 18 nucleotides (with 7 nucleotides flanking on each side of the tetra-loop sequence) of WT SDHB, TMEM109 and APP RNAs were folded using the Mfold nucleic acid folding program (). 18 nucleotides of WT PRPSAP2 RNA were folded using both Mfold and RNAfold 2.3.2 (; ). No optional parameters were used. A single structure along with the minimum free energy value for the structure was obtained for the selected RNAs and is represented in . […]
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