Project description:Human tumors show aberrant RNA profiles that can originate from multiple pathways and mechanisms. One underexplored area is that alterations in RNA decapping, the addition of a 5´-end N7-methyl guanosine (m7G)-cap that is essential for stabilization of the RNA molecule, could also be involved in the distorted transcript landscape of cancer cells. Herein we show that the RNA editing enzyme NUDT16 undergoes promoter CpG island methylation-associated silencing in T-cell acute lymphoblastic leukemia (T-ALL) cell lines and primary samples. The restoration of in vitro and in vivo NUDT16 activity highlights the growth inhibitory features of the gene. Most importantly, we identify that the epigenetic loss of NUDT16 in leukemia cells prevents the RNA decay of growth-promoting genes, among them the C-MYC stabilizers FBXO28 and USP37, leading to higher levels of the oncogenic protein.
Project description:Proteogenomic analysis and genomic profiling, RNA-sequencing, and mass spectrometry-based analysis of High hyperdiploid childhood acute lymphoblastic leukemia.
