Regulation ofthe core pre-mRNA splicing machinery by MYC and PRMT5 is essential to sustain lymphomagenesis [fetal liver]

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 E-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.

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Koh CM, Bezzi M, Low DH, Ang WX, Teo SX, Gay FP, Al-Haddawi M, Tan SY, Osato M, Sabò A, Amati B, Wee KB, Guccione E