The MTRR Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji B lymphoblastoid cell line, featuring targeted disruption of the MTRR gene. This gene encodes methionine synthase reductase (MSR), a key enzyme in cobalamin-dependent homocysteine remethylation. The polyclonal format provides a heterogeneous pool of edited cells, enabling functional interrogation of MTRR loss in a lymphoma-relevant background without clonal selection bias. This product is suitable for bulk population-based assays and pathway analysis.
Raji cells are an Epstein-Barr virus (EBV)-positive human Burkitt’s lymphoma line of B lymphocyte origin, expressing CD20 and widely used as a model for B-cell malignancies and immune cell research. Their transformed, fast-growing phenotype makes them particularly amenable to studies of metabolic vulnerabilities in cancer, including one-carbon metabolism and methionine dependency. The EBV-immortalized background also provides a context for investigating viral-host interactions with cellular metabolism.
MTRR catalyzes the reductive methylation of cobalamin to regenerate methylcobalamin, the active cofactor for methionine synthase (MTR). MTR subsequently remethylates homocysteine to methionine using 5-methyltetrahydrofolate as a methyl donor, connecting folate metabolism with the methionine cycle. This reaction is critical for maintaining cellular S-adenosylmethionine (SAM) pools, which serve as universal methyl donors for epigenetic modifications and biosynthesis. Disruption of MTRR impairs MTR activity, leading to accumulation of homocysteine and depletion of methionine and SAM. Key interacting factors include MTR itself, cobalamin, S-adenosylmethionine, flavin adenine dinucleotide (FAD), and NADPH. The pathway also involves MTHFR, CBS, BHMT, and methionine adenosyltransferases. MTRR function is regulated by SAM levels, dietary folate and vitamin B12 availability, and oxidative stress.
In the Raji B-cell lymphoma context, MTRR knockout offers a powerful tool to examine methionine dependency??a hallmark of many cancers??and the role of one-carbon metabolism in lymphomagenesis. Loss of MTRR is expected to exacerbate homocysteine accumulation and SAM depletion, potentially altering DNA and histone methylation patterns that control gene expression and genomic stability. This model can help dissect how B-cell lymphomas adapt to nutritional stress and identify metabolic checkpoints that are synthetic lethal with MTRR deficiency, thus informing targeted therapy strategies.
This polyclonal knockout pool is well-suited for a range of experimental applications, including investigation of folate/homocysteine metabolism in lymphoma, screening for small-molecule modulators of methionine synthase activity, and modeling the metabolic defects of cblE-type homocystinuria. Researchers can employ assays such as homocysteine ELISA, LC-MS/MS measurement of the SAM/SAH ratio, methionine synthase activity quantification, and Western blot or RT-qPCR to confirm MTRR disruption. Cell proliferation studies under methionine or folate restriction can reveal metabolic vulnerabilities, while global DNA methylation analysis (e.g., LINE-1 methylation) provides insights into epigenetic consequences. For further information or technical assistance, please contact Ascent Research.
