Regulation of the core pre-mRNA splicing machinery by MYC and PRMT5 is essential to sustain lymphomagenesis [B-cells]. Mus musculus

Over-expressed MYC binds to virtually all active promoters within a cell, although with different binding affinities, and modulates gene expression, both positively and negatively. Here, we show that during lymphomagenesis in Eµ-myc transgenic mice, MYC directly up-regulates the transcription of the core snRNP assembly genes, including PRMT5, an arginine methyltransferase, that methylates Sm proteins as an early step in lymphomagenesis. This coordinated regulatory effect is direct and is critical for snRNP biogenesis, the maintenance of effective mRNA splicing and cellular viability in cycling cells, in either fibroblasts or B-cells. Overall design: mRNA profiles of wild type and pre-tumoral eu-myc mice by deep sequencing, in triplicate, using Illumina NextSeq 500