Interferon-induced OASL restricts ADAR1 p150 RNA binding and A-to-I RNA editing
- 1Cleveland Clinic Research
Abstract
The interferon (IFN)-inducible RNA editor ADAR1 p150 catalyzes adenosine-to-inosine (A-to-I) editing of host and viral double-stranded RNAs, limiting aberrant innate immune sensing and regulating gene expression. How ADAR1 p150 activity is regulated during host-virus interactions remains poorly understood. Here, we identify the IFN-stimulated gene OASL as an inhibitor of ADAR1 p150. OASL engages p150 through two distinct interactions: its N-terminal OAS domain associates with the RNA-binding domains in an RNA-dependent manner, whereas its C-terminal ubiquitin-like domains bind the Z domain independently of RNA. Despite their distinct canonical functions, the OAS and ubiquitin-like domains converge to limit ADAR1 p150 RNA binding and suppress A-to-I editing across the transcriptome. OASL also reverses p150-mediated suppression of antiviral and innate immune gene expression and counteracts p150-mediated enhancement of measles virus and vesicular stomatitis virus replication. Thus, OASL restrains ADAR1 p150, linking interferon signaling to the control of RNA editing and antiviral immunity.
Related
- Short TALE-binding domains enable mitochondrial genome editing in Arabidopsis thaliana
- The C-terminus of the KREH1 helicase is important for RNA binding and association with mitochondrial RNA editing complexes in T. brucei
- ZBP1 specifically binds pre-formed Z-RNA, limiting its potential pool of nucleic acid ligands compared to ADAR1
- Structural Modeling Identifies a Conserved ADAR1 dsRBDIII Motif Predicted to Interact with PKR at Thr451
- Comparative ChIP-Seq Analysis of ERα Binding Induced by Estradiol, Zearalenone, and Bisphenol A in Human Ovarian Cells
BibTeX
@misc{quinonez2026interferoninduced,
title = {{Interferon-induced OASL restricts ADAR1 p150 RNA binding and A-to-I RNA editing}},
author = {S. Leon Quinonez and A. Gupta and S. Kang and Z. Jiang and C. C. Hsu and J. Li and F. Cheng and J. Jung},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.756717},
url = {https://www.biorxiv.org/content/10.64898/2026.10.05.756717v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Interferon-induced OASL restricts ADAR1 p150 RNA binding and A-to-I RNA editing
AU - S. Leon Quinonez
AU - A. Gupta
AU - S. Kang
AU - Z. Jiang
AU - C. C. Hsu
AU - J. Li
AU - F. Cheng
AU - J. Jung
PY - 2026
DA - 2026/10/05
PB - bioRxiv
DO - 10.64898/2026.10.05.756717
UR - https://www.biorxiv.org/content/10.64898/2026.10.05.756717v1
AB - The interferon (IFN)-inducible RNA editor ADAR1 p150 catalyzes adenosine-to-inosine (A-to-I) editing of host and viral double-stranded RNAs, limiting aberrant innate immune sensing and regulating gene expression. How ADAR1 p150 activity is regulated during host-virus interactions remains poorly understood. Here, we identify the IFN-stimulated gene OASL as an inhibitor of ADAR1 p150. OASL engages p150 through two distinct interactions: its N-terminal OAS domain associates with the RNA-binding domains in an RNA-dependent manner, whereas its C-terminal ubiquitin-like domains bind the Z domain independently of RNA. Despite their distinct canonical functions, the OAS and ubiquitin-like domains converge to limit ADAR1 p150 RNA binding and suppress A-to-I editing across the transcriptome. OASL also reverses p150-mediated suppression of antiviral and innate immune gene expression and counteracts p150-mediated enhancement of measles virus and vesicular stomatitis virus replication. Thus, OASL restrains ADAR1 p150, linking interferon signaling to the control of RNA editing and antiviral immunity.
ER -