bridge between this enzyme and transcription factors. Structure The yeast mediator complex is approximately as massive as a small subunit of a eukaryotic ribosome. The yeast mediator is composed of 25 subunits, while the mammalian mediator complexes are slightly larger. Mediator can be divided into 4 main parts: The head, middle, tail, and the transiently associated CDK8 kinase module. Mediator subunits have many intrinsically disordered regions called "splines", which may be important to allow the structural changes of the mediator that change the function of the complex. The figure shows how the splines of the Med 14 subunit connect a large portion of the complex together while still allowing flexibility. Mediator complexes that lack a subunit have been found or produced. These smaller mediators can still function normally in some activity, but lack other capabilities. This indicates a somewhat independent function of some of the subunits while being part of the larger complex. Another example of structural variability is seen in vertebrates, in which 3 paralogues of subunits of the cyclin-dependent kinase module have evolved by 3 independent gene duplication events followed by sequence divergence. There is a report that mediator forms stable associations with a particular type of non-coding RNA, ncRNA-a. These stable associations have also been shown to regulate gene expression in vivo, and are prevented by mutations in MED12 that produce the human disease FG syndrome. Thus, the structure of a mediator complex can be augmented by RNA as well as proteinaceous transcription factors. Function Mediator was originally discovered because it was important for RNA polymerase II function, but it has many more functions than just interactions at the transcription start site. RNA polymerase II-Mediator core initiation complex Mediator is a crucial component for transcription initiation. Mediator interacts with the pre-initiation complex, composed of RNA Polymerase II and general transcription factors TFIIB, TFIID, TFIIE, TFIIF, and TFIIH to stabilize and initiate transcription. Studies of Mediator-RNA Pol II contacts in budding yeast have emphasized the importance of TFIIB-Mediator contacts in the formation of the complex. Interactions of Mediator with TFIID in the initiation complex has been shown. The Structure of a core Mediator (cMed) that's associated with a core pre-initiation complex was elucidated. RNA synthesis The preinitiation complex, which contains mediator, transcription factors, a nucleosome and RNA polymerase II, is important to position the polymerase for the start of transcription. Before RNA synthesis can occur, the polymerase must