The DIS3L Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the K-562 human chronic myelogenous leukemia line, targeting the DIS3L gene. This loss-of-function model disrupts the 3′-5′ exoribonuclease catalytic subunit of the cytoplasmic RNA exosome, enabling functional studies of cytoplasmic mRNA degradation and surveillance in a leukemic background.
The host K-562 cell line originates from a human female with BCR-ABL1-positive, p53-null CML blast crisis. Grown in suspension, these lymphoblasts are widely employed as a model for leukemia, hematopoiesis, NK cell cytotoxicity, and erythroid differentiation, providing a physiologically relevant context for investigating post-transcriptional regulation in malignancy.
DIS3L acts as the catalytic exonuclease of the cytoplasmic RNA exosome, executing 3′-5′ degradation of mRNA substrates. It physically associates with exosome core subunits EXOSC3 and EXOSC6, and the SKI complex components SKIV2L and TTC37 to mediate RNA surveillance. DIS3L activity is modulated by BCR-ABL signaling and the MYC oncoprotein, and its downstream targets include MYC, CCND1, and BCL2 family mRNAs. Knockout of DIS3L disrupts this decay machinery, potentially leading to aberrant stabilization of oncogenic transcripts.
In the K-562 leukemic context, impaired cytoplasmic RNA turnover through DIS3L disruption is predicted to affect cell proliferation, apoptosis, and drug sensitivity. This model thus links RNA metabolic pathways with BCR-ABL-driven leukemogenesis and is pertinent to multiple myeloma and other hematologic malignancies where DIS3L mutations are reported.
Research applications include identifying DIS3L-regulated mRNAs via RNA-seq and actinomycin D chase assays, measuring transcript half-lives by RT-qPCR, and probing exosome complex integrity through co-immunoprecipitation of EXOSC3 or SKIV2L. Functional phenotyping with MTS/MTT proliferation, Annexin V apoptosis, flow cytometric cell cycle analysis, and imatinib IC50 determinations enable detailed characterization. The model also supports drug sensitization studies and synthetic lethality screens. For further technical information, please contact Ascent Research.
