ADBP-1 regulates ADR-2 nuclear localization to control editing substrate selection

Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by ADAR enzymes, is a prevalent and conserved RNA modification. While A-to-I RNA editing is essential in mammals, in Caenorhabditis elegans, it is not, making them invaluable for RNA editing research. ADR-2 is the sole A-to-I editing enzyme in C. elegans. Although ADAR localization and function are well studied in human, adr-2 localization and function is not established in C. elegans. In this study, we first examine the cellular and tissue-specific localization of ADR-2. Using an ADR-2 antibody, we showed that while ADR-2 is present in most cells in the embryo, at later stages, the expression is both tissue- and cell-type-specific. Our results indicate that ADR-2 is mainly in the nucleus, where it is adjacent to the chromosomes at all cell cycle stages. Consistent with previous research, we showed that ADR-2 nuclear localization depends on ADBP-1. In contrast, we showed that ADR-2 does not depend on ADR-1, a prominent RNA editing regulator in C. elegans. These observations suggest RNA editing is a co-transcriptional modification that occurs mainly in the nucleus with a cell-and tissue-specific pattern. Our computational analysis showed that in adbp-1 mutant worms, the amount of editing sites decreases significantly, and most reside in exons. Furthermore, the lack of ADR-2 regulation leads to new editing site creation, which does not exist in wild-type worms, and affects the expression of lncRNAs and 3`UTR edited genes, mainly at the embryonic stage.