Z-Form Stabilization By The Zα Domain Of Adar1p150 Has Subtle Effects On A-To-I Editing

Previous studies on Zα mutations faced limitations, including variable ADAR1p150 expression, differential editing analysis challenges, and unaccounted changes in ADAR1p150 localization. To address these issues, we developed a Cre-lox system in ADAR1p150 KO cells to generate stable cell lines expressing Zα mutant ADAR1p150 constructs.

Using total RNA sequencing analyzing editing clusters as a proxy for dsRNAs, we found that Zα mutations slightly decreased overall A-to-I editing, consistent with recent findings. These decreases correlated with mislocalization of ADAR1p150 rather than reduced editing specificity, and practically no statistically significant differentially edited sites were identified between wild-type and Zα mutant ADAR1p150 constructs.