A transcriptome-wide systematic search does not detect A-to-I RNA editing in cis-antisense RNA duplexes
- Zohar Rosenwasser1,2,
- Roni Cohen-Fultheim1,2,
- Ofir Shliefer1,2,
- Erez Y. Levanon1,2,4 and
- Eli Eisenberg3,4
- 1Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel;
- 2The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan 5290002, Israel;
- 3Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv 6997801, Israel
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↵4 These authors contributed equally to this work.
Abstract
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 examine 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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.280820.125.
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Freely available online through the Genome Research Open Access option.
- Received April 20, 2025.
- Accepted March 2, 2026.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
