In Prmt5-deficient mouse neural progenitor and human B cell lymphoma cells, p53 activation is partly caused by altered splicing producing an unstable form of the negative p53 regulator Mdm419,25, which we observe in Prmt5-null B cells but does not explain the p53-independent effects. The gene discussed is PRMT5; the disease is B-cell non-Hodgkin lymphoma.