The Ess1 prolyl isomerase is linked to chromatin remodeling complexes and the general transcription machinery

The Ess1/Pin1 peptidyl-prolyl isomerase (PPIase) is thought to control mito sis by binding to cell cycle regulatory proteins and altering their activit y. Here we isolate temperature-sensitive ess1 mutants and identify six mult icopy suppressors that rescue their mitotic-lethal phenotype, None are cell cycle regulators. Instead, five encode proteins involved in transcription that bind DNA, modify chromatin structure or are regulatory subunits of RNA polymerase II. A sixth suppressor, cyclophilin A, is a member of a distinc t family of PPIases that are targets of immunosuppressive drugs. We show th at the expression of some but not all genes is decreased in ess1 mutants, a nd that Ess1 interacts with the C-terminal domain (CTD) of RNA polymerase I I in vitro and in vivo, The results forge a strong link between PPIases and the transcription machinery and suggest a new model for how Ess1/Pin1 cont rols mitosis. In this model, Ess1 binds and isomerizes the CTD of RNA polym erase II, thus altering its interaction with proteins required for transcri ption of essential cell cycle genes.