Interferon-induced OASL restricts ADAR1 p150 RNA binding and A-to-I RNA editing

Leon Quinonez, S.; Gupta, A.; Kang, S.; Jiang, Z.; Hsu, C. C.; Li, J.; Cheng, F.; Jung, J.

doi:10.64898/2026.10.05.756717

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bioRxiv · 10.64898/2026.10.05.756717

Interferon-induced OASL restricts ADAR1 p150 RNA binding and A-to-I RNA editing

Leon Quinonez, S.·Gupta, A.·Kang, S.·Jiang, Z.·Hsu, C. C.·Li, J.·Cheng, F.·Jung, J.

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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.

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Leon Quinonez, S., Gupta, A., Kang, S., Jiang, Z., Hsu, C. C., Li, J., Cheng, F., Jung, J.. 2026-10-06. Interferon-induced OASL restricts ADAR1 p150 RNA binding and A-to-I RNA editing. https://doi.org/10.64898/2026.10.05.756717

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