Genome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB-dependent IFITM3 expression.

Autor:	Munir M; Departments of Immunology and Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Embry A; Departments of Immunology and Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Doench JG; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Heaton NS; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA., Wilen CB; Department of Laboratory Medicine and Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA., Orchard RC; Departments of Immunology and Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address: Robert.Orchard@UTSouthwestern.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Apr; Vol. 300 (4), pp. 107153. Date of Electronic Publication: 2024 Mar 09.
DOI:	10.1016/j.jbc.2024.107153
Abstrakt:	The innate immune system features a web of interacting pathways that require exquisite regulation. To identify novel nodes in this immune landscape, we conducted a gain-of-function, genome-wide CRISPR activation screen with influenza A virus. We identified both appreciated and novel antiviral genes, including Jade family PHD zinc finger 3 (JADE3) a protein involved in directing the histone acetyltransferase histone acetyltransferase binding to ORC1 complex to modify chromatin and regulate transcription. JADE3 is both necessary and sufficient to restrict influenza A virus infection. Our results suggest a distinct function for JADE3 as expression of the closely related paralogs JADE1 and JADE2 does not confer resistance to influenza A virus infection. JADE3 is required for both constitutive and inducible expression of the well-characterized antiviral gene interferon-induced transmembrane protein 3 (IFITM3). Furthermore, we find JADE3 activates the NF-kB signaling pathway, which is required for the promotion of IFITM3 expression by JADE3. Therefore, we propose JADE3 activates an antiviral genetic program involving NF-kB-dependent IFITM3 expression to restrict influenza A virus infection. Competing Interests: Conflict of interest The authors declare that they have no conflict of interests with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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