A Protein-Protein Interaction Underlies the Molecular Basis for Substrate Recognition by an Adenosine to Inosine RNA Editing Enzyme

We report an unbiased analysis of ADR-2 binding across the C. elegans transcriptome, which indicates that ADR-1 is required for ADR-2 to stably bind a majority of target mRNAs in vivo. By obtaining 30-50 million reads from immunoprecipitated RNA and input samples from wild type and adr-2(-) strains, we identified 1235 ADR-2 bound targets in wild-type worms. Comparing these ADR-2 bound targets with a list of all known edited targets in C. elegans, we determined ~65% of them are edited. Additionally sequencing reads from an ADR-2 RIP assay performed in the adr-1(-) strain were used to determine that the majority of ADR-2 targets (80%) have significantly reduced binding by ADR-2 in the absence of adr-1. ADR-2 RIP-seq in WT, adr-2(-) and adr-1(-) was performed in duplicates, using Illumina NextSeq500 along with RNA-seq of input lysates from the above three strains.