We found that A3A binds to RNA in a highly specific and structural context-dependent manner. Previous reports19 suggested that A3A bound only weakly and did not deaminate RNA. However, the potential substrate sequence was designed to lack secondary structure, which in light of our results on hairpin versus linear RNAs, may have inadvertently precluded RNA deamination. Recently, A3G and A3A were implicated in deaminating RNA in proposed RNA hairpins in whole cell lysates but the specificity was not quantified35,37. Intriguingly, our data show that A3A binds RNA hairpins with similar affinity as for DNA hairpins, which suggests that RNA-editing activity of A3A might be more prevalent than previously anticipated. Future experiments will identify if A3A’s catalytic efficiency is similar for DNA and RNA hairpins.