Ubiquitin is a small protein that was initially found to function as a tag that can be covalently attached to proteins to mark them for destruction by a multisubunit, adenosine 5′-triphosphate–dependent protease called the proteasome. Ubiquitin is now emerging as a key regulator of eukaryotic messenger RNA synthesis, a process that depends on the RNA synthetic enzyme RNA polymerase II and the transcription factors that control its activity. Ubiquitin controls messenger RNA synthesis not only by mechanisms involving ubiquitin-dependent destruction of transcription factors by the proteasome, but also by an intriguing collection of previously unknown and unanticipated mechanisms that appear to be independent of the proteasome.