A CRISPR-Cas9 knockout screening identifies IRF2 as a key driver of OAS3/RNase L-mediated RNA decay during viral infection.

Autor:	Oh S; Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697., Santiago G; Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697., Manjunath L; Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697., Li J; Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697., Bouin A; Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697., Semler BL; Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697., Buisson R; Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Nov 05; Vol. 121 (45), pp. e2412725121. Date of Electronic Publication: 2024 Oct 30.
DOI:	10.1073/pnas.2412725121
Abstrakt:	OAS-RNase L is a double-stranded RNA-induced antiviral pathway triggered in response to diverse viral infections. Upon activation, OAS-RNase L suppresses virus replication by promoting the decay of host and viral RNAs and inducing translational shutdown. However, whether OASs and RNase L are the only factors involved in this pathway remains unclear. Here, we develop CRISPR-Translate, a FACS-based genome-wide CRISPR-Cas9 knockout screening method that uses translation levels as a readout and identifies IRF2 as a key regulator of OAS3. Mechanistically, we demonstrate that IRF2 promotes basal expression of OAS3 in unstressed cells, allowing a rapid activation of RNase L following viral infection. Furthermore, IRF2 works in concert with the interferon response through STAT2 to further enhance OAS3 expression. We propose that IRF2-induced RNase L is critical in enabling cells to mount a rapid antiviral response immediately after viral infection, serving as the initial line of defense. This rapid response provides host cells the necessary time to activate additional antiviral signaling pathways, forming secondary defense waves. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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