RNA binding by ADARs prevents RNA interference from attacking self-produced dsRNA
- 1Faculty of Biology, Technion–Israel Institute of Technology, Technion City, Haifa 32000, Israel.
- 2Technion Center for Structural Biology (TCSB), Technion Human Health Initiative (THHI), Technion–Israel Institute of Technology, Haifa, Israel.
- 3Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Abstract
The ability of an organism to distinguish between self and foreign double-stranded RNA (dsRNA) is central to eliciting an immune response when needed while preventing autoimmunity. Using Caenorhabditis elegans, we investigated the interplay between two host pathways that regulate dsRNA expression and function, adenosine-to-inosine RNA editing by adenosine deaminases that act on RNA (ADARs), and RNA interference (RNAi). We found that the number of small interfering RNAs (siRNAs) targeting edited genes is significantly up-regulated in ADAR mutant animals. In addition, despite an almost complete depletion of primary siRNAs generated from editing sites in wild-type animals, secondary siRNAs are generated from edited transcripts, suggesting that ADARs antagonize only the first step of RNAi processing. We show that ADARs interfere with the efficacy of exogenous RNAi in vivo, likely to prevent trans-silencing, and provide evidence that ADR-2 binding to dsRNA is required for efficient RNAi suppression. This work sheds light on how RNA editing safeguards self-dsRNAs against immune recognition and by-product degradation.
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BibTeX
@article{ganem2026binding,
title = {{RNA binding by ADARs prevents RNA interference from attacking self-produced dsRNA}},
author = {Nabeel S. Ganem and Dean Light and Roni Haas and Boaz Goldstein and Alla Fishman and Yahav Festinger and Noa Ben-Asher and Orna Ben-Naim Zgayer and Berta Eliad and Fabian Glaser and Suba Rajendren and Heather A. Hundley and Ayelet T. Lamm},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aed7314},
url = {https://www.science.org/doi/abs/10.1126/sciadv.aed7314},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - RNA binding by ADARs prevents RNA interference from attacking self-produced dsRNA
AU - Nabeel S. Ganem
AU - Dean Light
AU - Roni Haas
AU - Boaz Goldstein
AU - Alla Fishman
AU - Yahav Festinger
AU - Noa Ben-Asher
AU - Orna Ben-Naim Zgayer
AU - Berta Eliad
AU - Fabian Glaser
AU - Suba Rajendren
AU - Heather A. Hundley
AU - Ayelet T. Lamm
PY - 2026
DA - 2026/10/30
JO - Science Advances
DO - 10.1126/sciadv.aed7314
UR - https://www.science.org/doi/abs/10.1126/sciadv.aed7314
AB - The ability of an organism to distinguish between self and foreign double-stranded RNA (dsRNA) is central to eliciting an immune response when needed while preventing autoimmunity. Using Caenorhabditis elegans, we investigated the interplay between two host pathways that regulate dsRNA expression and function, adenosine-to-inosine RNA editing by adenosine deaminases that act on RNA (ADARs), and RNA interference (RNAi). We found that the number of small interfering RNAs (siRNAs) targeting edited genes is significantly up-regulated in ADAR mutant animals. In addition, despite an almost complete depletion of primary siRNAs generated from editing sites in wild-type animals, secondary siRNAs are generated from edited transcripts, suggesting that ADARs antagonize only the first step of RNAi processing. We show that ADARs interfere with the efficacy of exogenous RNAi in vivo, likely to prevent trans-silencing, and provide evidence that ADR-2 binding to dsRNA is required for efficient RNAi suppression. This work sheds light on how RNA editing safeguards self-dsRNAs against immune recognition and by-product degradation.
SN - 2375-2548
ER -