A study shows how Caffeine regulates alternative splicing in a subset cancer-associated genes including the transcription factor and tumor suppressor KLF6 through the splicing factor SC35. There is a necessary “caffeine response element” in the intron of KLF6 which plays a role in the splice-site choice, although caffeine induces up-regulation of SC35 and over-expression of SC35 is sufficient to mimic the caffeine response.