The DUS3L Knockout 786-O Polyclonal Cells product offers a CRISPR/Cas9-edited polyclonal knockout cell population for loss-of-function studies of DUS3L in the human renal cell adenocarcinoma line 786-O. This polyclonal population harbors heterogeneous gene disruptions across the cell pool, providing a robust model that reflects the genetic diversity of the host line without requiring clonal isolation. It is designed to facilitate investigations into tRNA modification and its role in translation regulation within a cancer context.
The 786-O cell line is derived from a primary clear cell renal cell carcinoma and carries a biallelic VHL mutation. This inactivation of the von Hippel-Lindau tumor suppressor leads to constitutive stabilization of hypoxia-inducible factors (HIF), which drive a pseudohypoxic transcriptional program. Consequently, 786-O cells upregulate genes involved in angiogenesis, metabolism, and proliferation, making the line a relevant model for studying VHL/HIF-dependent tumor biology in renal cell carcinoma.
DUS3L encodes a tRNA-dihydrouridine synthase that catalyzes the site-specific reduction of uridine to dihydrouridine in tRNA molecules. This modification is essential for proper tRNA folding, stability, and accurate codon?Canticodon pairing during translation. The DUS3L pathway includes tRNA substrates, dihydrouridine, ribosomal components, and translation factors, collectively ensuring translation fidelity and global protein synthesis. Disruption can cause proteome changes and affect cell proliferation.
Within the 786-O cellular environment, constitutive HIF activity imposes a high demand for robust protein synthesis to sustain oncogenic phenotypes. Loss of DUS3L may compromise the translational machinery, potentially attenuating cell growth and tumorigenic capacity. This polyclonal knockout model thus provides a powerful system for dissecting how tRNA modifications contribute to the translation-dependent processes that drive renal cell carcinoma progression.
This knockout product is suitable for functional studies of tRNA dihydrouridylation, translation regulation in cancer, and target evaluation. Assays include PCR, RT-qPCR, western blotting, tRNA dihydrouridine analysis, puromycin incorporation, proliferation and colony formation assays, and flow cytometry. Contact Ascent Research for inquiries.
