Structure of mammalian Mediator complex reveals Tail module architecture and interaction with a conserved core.

The Mediator complex plays an essential and multi-faceted role in regulation of RNA polymerase II transcription in all eukaryotes. Structural analysis of yeast Mediator has provided an understanding of the conserved core of the complex and its interaction with RNA polymerase II but failed to reveal the structure of the Tail module that contains most subunits targeted by activators and repressors. Here we present a molecular model of mammalian (Mus musculus) Mediator, derived from a 4.0 A resolution cryo-EM map of the complex. The mammalian Mediator structure reveals that the previously unresolved Tail module, which includes a number of metazoan specific subunits, interacts extensively with core Mediator and has the potential to influence its conformation and interactions. The Mediator complex regulates RNA polymerase II transcription in all eukaryotes. The mammalian Mediator cryo-EM structure reveals the architecture of previously unresolved Tail module and suggests its regulatory role in the complex conformation and interactions.