The PARP9 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the Raji B lymphocyte line, designed for loss-of-function studies of PARP9. This heterogeneous pool of gene-disrupted cells enables robust functional analyses without clonal selection, providing a versatile tool for investigating PARP9-dependent processes.
Raji is an EBV-positive Burkitt lymphoma cell line from a pediatric male patient, widely used as a model for B cell lymphoma, EBV latency, and B cell receptor signaling. These cells maintain active JAK-STAT signaling and interferon responsiveness, making them an ideal host for studying innate immune pathways in a lymphoma context.
PARP9 is an interferon-inducible macrodomain reader of ADP-ribosylation. Following interferon-??/??/?? binding to receptors IFNAR1/IFNAR2, JAK1/TYK2 kinases phosphorylate STAT1/STAT2, which dimerize with IRF9 to induce PARP9 expression. PARP9 partners with the E3 ubiquitin ligase DTX3L to ubiquitinate histone H2B, modulating interferon-stimulated gene (ISG) transcription (e.g., ISG15, MX1). The PARP9?CDTX3L complex also influences DNA damage responses through interactions with PARP1 and ADP-ribosylated substrates. Additionally, PARP9 functions downstream of cytosolic nucleic acid sensors RIG-I, MDA5, cGAS, and STING, linking to TBK1 and IRF3/IRF7 antiviral signaling.
Knockout of PARP9 in Raji cells provides a system to dissect ADP-ribosylation-dependent regulation of antiviral innate immunity and lymphoma biology. The model allows investigation of how PARP9?CDTX3L-mediated histone ubiquitination impacts ISG expression, STAT1 phosphorylation kinetics, and cellular responses to interferon stimulation. This is particularly relevant for understanding immune evasion mechanisms in EBV-driven B cell malignancies and for evaluating the role of ubiquitin-proteasome crosstalk in DNA repair.
Applications include RT-qPCR or RNA-seq profiling of interferon-stimulated genes, phospho-STAT1 flow cytometry, co-immunoprecipitation of DTX3L complexes, and histone ubiquitination assays. Antiviral activity can be assessed via VSV-GFP infection, while cell viability and apoptosis assays reveal lymphoma cell dependencies. This polyclonal knockout is suitable for drug target validation in inflammatory and viral diseases and for functional genomics of B cell lymphomas. For further information, please contact Ascent Research.
