Highlights d Inhibition of SDMA or ADMA preferentially kills splicing factor (SF)-mutant cells d Combined inhibition of PRMT5 and type I PRMTs has synergistic effects d RNA-binding proteins are the most enriched cellular substrates of PRMTs d Inhibition of RNA splicing underlies the cytotoxic effects of PRMT inhibition

MBNL1 proteins lacking exon 7 (−ex7) are antisurvival factors with tumor suppressive role that cancer cells tend to down-regulate in favor of MBNL +ex7 isoforms.