Epitranscriptome-wide profiling identifies RNA editing events regulated by ADAR1 that are associated with DNA repair mechanisms in human TK6 cells.

Introduction: Adenosine-to-Inosine (A-to-I) editing is an endogenous RNA modification in eukaryotes, catalyzed by adenosine deaminases acting on RNA (ADARs). This modification modulates the gene expression by influencing splicing, RNA stability, and coding potential, depending on the site of editing. Although recent studies suggest a crosstalk between A-to-I editing and transcripts involved in DNA repair, the extent and functional significance of this interaction remain unclear. Methods: To investigate this, we applied the EpiPlex RNA assay-a method enabling epitranscriptome-wide detection of RNA modifications-in human lymphoblastoid TK6 cells. Results: Across two biological replicates, we identified 870 transcripts bearing A-to-I-modifications. Gene Ontology analysis revealed significant enrichment in genome maintenance pathways, including "chromatin remodeling" and "DNA repair." Notably, 27 transcripts encoding DNA repair proteins-such as Discussion: Our epitranscriptomic analysis of A-to-I RNA editing underscores a multifaceted role for ADAR1-dependent editing in preserving genome integrity through post-transcriptional regulation of DNA repair genes, laying the groundwork for future studies into RNA-based mechanisms of genome maintenance.