Abstract
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 Å 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.
Highlights
The Mediator complex plays an essential and multi-faceted role in regulation of RNA polymerase II transcription in all eukaryotes
Secondary structure elements were clearly resolved throughout the cryo-EM map and densities for bulky amino acid side chains were apparent throughout MED14, the lower portion of the helical bundle formed by MED11–MED22 (Head) module, and the Tail module
We previously reported results from EM analysis of mammalian Mediator (mMED) subunit deletion mutants showing that release of Middle–Tail interactions by deletion of MED1, or disruption of the Tail’s integrity by deletion of Tail subunits, resulted in increased Mediator–RNA polymerase II (RNAPII) interaction[14]
Summary
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. 1234567890():,; Mediator, a large multi-protein complex first identified in budding yeast as an agent required to convey regulatory information to the basal transcription machinery[1,2,3], plays an essential and multi-faceted role in regulation of RNA polymerase II (RNAPII) transcription in all eukaryotes[4,5]. We recently determined an intermediate (6 Å) resolution cryo-EM structure of mMED that provided insight into its molecular organization, explored the function of Tail subunits, and clarified the role of Mediator in enhancer–promoter contacts[14]. The model shows how metazoan-specific subunits have been integrated and add to the complexity of mMED organization, influencing its conformation and interactions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
