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

• Published in: Nucleic acids research 2024-09, Vol.52 (16), p.9501-9518
• Main Authors: Eliad, Berta, Schneider, Noa, Ben-Naim Zgayer, Orna, Amichan, Yarden, Glaser, Fabian, Erdmann, Emily A, Rajendren, Suba, Hundley, Heather A, Lamm, Ayelet T
• Format: Article
• Language: English
• Subjects: Adenosine Deaminase - genetics; Adenosine Deaminase - metabolism; Animals; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Nucleus - genetics; Cell Nucleus - metabolism; Gene regulation, Chromatin and Epigenetics; Mutation; RNA Editing; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Substrate Specificity
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkae641

Abstract 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. In C. elegans, ADR-2 is the sole catalytic A-to-I editing enzyme, and ADR-1 is an RNA editing regulator. ADAR localization is well-studied in humans but not well-established in C. elegans. In this study, we examine the cellular and tissue-specific localization of ADR-2. We show that while ADR-2 is present in most cells in the embryo, at later developmental stages, its expression is both tissue- and cell-type-specific. Additionally, both ADARs are mainly in the nucleus. ADR-2 is adjacent to the chromosomes during the cell cycle. We show that the nuclear localization of endogenous ADR-2 depends on ADBP-1, not ADR-1. In adbp-1 mutant worms, ADR-2 is mislocalized, while ADR-1 is not, leading to decreased editing levels and de-novo editing, mostly in exons, suggesting that ADR-2 is also functional in the cytoplasm. Besides, mutated ADBP-1 affects gene expression. Furthermore, we show that ADR-2 targets adenosines with different surrounding nucleotides in exons and introns. Our findings indicate that ADR-2 cellular localization is highly regulated and affects its function. Graphical Abstract Graphical Abstract