Transcriptome-wide systematic search does not detect A-to-I RNA editing in cis -antisense RNA duplexes

A-to-I RNA editing, catalyzed by the adenosine deaminase acting on RNA (ADAR) enzymes, is a posttranscriptional process that modifies RNA sequences and diversifies the transcriptome. ADARs bind to double-stranded RNA (dsRNA) and their specificity and efficiency are affected by the structural properties of these substructures. In most cases, the dsRNA structure arises from homology between two segments of the same RNA molecule that fold into RNA stem structures. Another possible source of dsRNA is cotranscription of sense and antisense strands of the same genomic region. Binding of these complementary, naturally occurring, antisense transcripts (NATs) results in a perfect RNA duplex, which may be targeted by ADARs. To explore the scope of ADAR editing of NAT-derived dsRNA, we examined editing levels at genome locations where both strands are transcribed. Our findings indicate that editing is rare in regions for which both strands cotranscribe. Moreover, even when RNA editing does occur in NAT regions, it is typically associated with secondary structures on a single strand, suggesting that editing depends on intramolecular structures rather than binding of NATs.