In multiple disease states ranging from cancer to viral infection, the mechanisms of general transcription are altered. In order to understand the extent of disease manipulation of the transcription machinery, general mechanisms that control transcription under normal conditions must be understood. We apply quantitative proteomic and genomic techniques to study the dynamics of RNA Polymerase II transcription. Using Multidimentional Protein Indentification Technology (MudPIT), we can study both protein-protein interaction networks and post-translational modifications that may alter transcription during different cellular states. During RNA Polymerase II transcription, the C-terminal domain (CTD) of Rpb1 has been proposed to act as a scaffold to coordinate transcription initiation, elongation, termination, histone modification, and mRNA processing events. These events have been shown to correlate with distinct changes in the pattern of CTD phosphorylation across open reading frames. The major focus of our research is to study the role of the CTD phosphatase Rtr1 during the transcription cycle and to understand how alterations in the phosphorylation state of the CTD influence gene expression and mRNA processing.