DEAD-box RNA helicase 18 disrupts IRF3-binding to the interferon-β promoter

Xiao, S.; Xiao, X.; Wang, M.; Zhao, W.; Fang, P.; Zhou, Y.; Wang, D.; Fang, L.

doi:10.1101/2021.10.26.465893

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bioRxiv · 10.1101/2021.10.26.465893

DEAD-box RNA helicase 18 disrupts IRF3-binding to the interferon-β promoter

Xiao, S.·Xiao, X.·Wang, M.·Zhao, W.·Fang, P.·Zhou, Y.·Wang, D.·Fang, L.

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Abstract

The production of type I interferons (IFN-/{beta}) requires strict control to avoid excessive activation during viral infections. The binding of interferon regulatory factor 3 (IRF3) to the IFN-{beta} promoter region in the nucleus is essential for IFN-{beta} transcription; however, whether nuclear factors have important negative-regulatory roles in this process is largely unknown. By screening for IRF3-interacting partners in the nucleus, we identified DEAD-box RNA helicase 18 (DDX18) as an important negative regulator of intranuclear IRF3. Overexpression of DDX18 suppressed virus- and IRF3-induced IFN-{beta} production, whereas knockdown of DDX18 expression or knockout of the DDX18 gene had opposite effects. Mechanistically, DDX18 interacts with IRF3 and decreases the binding of IRF3 to the IFN-{beta} promoter after viral infection. DDX18 knockdown mice (Ddx18+/-) further demonstrated that DDX18 suppressed antiviral innate immunity in vivo. Thus, despite many members of the DDX family act as important positive regulators in the cytoplasm, DDX18 plays a unique "braking" role in balancing virus-induced type I IFN production.

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Xiao, S., Xiao, X., Wang, M., Zhao, W., Fang, P., Zhou, Y., Wang, D., Fang, L.. 2021-10-28. DEAD-box RNA helicase 18 disrupts IRF3-binding to the interferon-β promoter. https://doi.org/10.1101/2021.10.26.465893

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