The DIS3L2 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji B lymphocyte lineage, providing a robust loss-of-function model for investigating the 3′-5′ exoribonuclease DIS3L2. This product comprises a heterogeneous pool of edited cells with targeted disruption of the DIS3L2 gene, enabling researchers to study the functional consequences of DIS3L2 deficiency in a well-characterized human cell background without the need for isolating single-cell clones. The polyclonal format preserves population-level heterogeneity while eliminating wild-type DIS3L2 expression, making it suitable for assays where bulk cell behavior reflects the knockout phenotype.
The Raji host cell line originates from a patient with Burkitt lymphoma and is widely employed in immunology and oncology research. These cells are Epstein-Barr virus (EBV)-positive B lymphocytes that retain features of mature B cells, including antibody production and participation in adaptive immune responses. Raji cells express key B cell markers and exhibit rapid proliferation, facilitating experimental scalability. Their derivation from a lymphoma background renders them particularly valuable for dissecting molecular mechanisms in B-cell malignancies and assessing gene function in a cancer-relevant context.
DIS3L2 functions as a critical exoribonuclease in the RNA surveillance pathway, selectively degrading uridylated RNA substrates. The enzyme is recruited to target RNAs through the terminal uridylation activity of upstream regulators TUT4 (ZCCHC6) and TUT7 (ZCCHC11), which add uridine tails to pre-miRNAs and mature miRNAs. In the LIN28-TUT4-DIS3L2 axis, LIN28A and LIN28B facilitate TUT4/7-mediated uridylation of pre-let-7, marking it for DIS3L2-dependent decay, thereby preventing mature let-7 miRNA production. Conversely, DIS3L2 also degrades uridylated mature miRNAs such as let-7, establishing a multi-layered post-transcriptional regulatory network. Knockout of DIS3L2 leads to accumulation of uridylated RNA species, shifting miRNA profiles and altering downstream gene expression networks.
In Raji B lymphocytic cells, DIS3L2 ablation has particular relevance for RNA decay and miRNA turnover, processes intimately linked to lymphocyte development and oncogenesis. Deregulation of miRNA homeostasis is a hallmark of Burkitt lymphoma and other B-cell malignancies, and DIS3L2 has been associated with Wilms tumor susceptibility and Perlman syndrome, disorders involving disordered RNA metabolism. The knockout model allows investigation of how uridylated RNA accumulation impacts B-cell proliferation, survival, and transformation, providing a platform for dissecting the interplay between post-transcriptional control and lymphomagenesis. This model may recapitulate aspects of disease-relevant RNA dysregulation seen in cancers with impaired DIS3L2 function.
Research applications include miRNA turnover studies, RNA decay pathway analysis, and functional genomics in B-cell cancer models. Users can employ small RNA sequencing and RNA-seq to profile changes in uridylated RNA accumulation and transcriptome-wide effects. Western blotting and RT-qPCR confirm DIS3L2 protein loss and downstream target expression. Cell proliferation and apoptosis assays reveal phenotypic consequences of DIS3L2 knockout in lymphoma cells. This product supports investigations into LIN28B-TUT4-DIS3L2 signaling, post-transcriptional regulation of let-7 family miRNAs, and development of therapeutic strategies targeting RNA surveillance pathways. For detailed information on product specifications and technical support, please contact Ascent Research.
