The function of a protein is governed by its interaction with other proteins inside a cell. Therefore, it is important to identify the interacting partners of a particular protein to decipher its function. The protein interaction networks are generally determined by bioinformatic as well as experimental methodologies such as yeast two hybrid, mass spectrometry, immunoprecipitation, and fluorescence resonance energy transfer assays. Here, we have analyzed bioinformatically the interactions of Rpb1p (the largest subunit of RNA Polymerase II) with other proteins in yeast, using Cytoscape software and Biogrid/Biomart database. We find that Rpb1p interacts with a large number of proteins involved in mRNA synthesis, processing, export, and other cellular processes. These results validate the application of such bioinformatic approach to determine the interactome for other cellular proteins.