Alli Schier

Structure and Function of the CDK8 Module

My project focuses on how the CDK8 Module is regulating transcription. The CDK8 module reversibly associates with Mediator and is responsible for transcription regulation, but not much is known about how its four protein subunits (CDK8 kinase, CCNC, MED12, and MED13) associate. The CDK8 kinase-CCNC dimer is responsible for regulating Mediator function though phosphorylation of the transcription machinery, including DNA-binding transcription factors, the RNA polymerase II C-terminal domain, and histones, among others. The MED12 and MED13 subunits are key regulatory components of the module, responsible for regulating CDK8 kinase activity and association with Mediator. Little structural data are available for them and thus little is known about how the entire CDK8 module interacts with the greater Mediator structure. This structural information complemented with functional studies will be paramount in determining how the CDK8 module affects Mediator function in transcription regulation and could have implications in human development and disease, such as cancer. 

 

Publications

Schier, AC; Taatjes, DJ. Everything at once: Cryo-EM yields remarkable insights about human RNA polymerase II transcription. Nat Struct Mol Biol 2021, 28: 540 - 543.   

Schier, AC; Taatjes, DJ. Structure and mechanism of the RNA polymerase II transcription machinery. Genes Dev. 2020, 34: 465 – 488.