Our goal is to understand the mechanism of transcription and its regulation. Determining structures of RNA polymerase and transcription complexes is an essential step. Because of their large size and complexity determination of these structures will require a combination of electron microscopy, biophysical methods, and biochemical methods to identify functionally and structurally relevant subassemblies and domains and x-ray crystallography to determine high-resolution structures of RNA polymerase components and accessory factors. We recently solved the 2.5-Angstrom crystal structure of the Escherichia coli RNA polymerase a subunit N-terminal domain, which is the first high-resolution structure of a core component required for RNA polymerase assembly and basal transcription. This structure, combined with a new 19-Angstrom resolution structure determined by cryo-electron microscopy of helical crystals of E. cold core RNAP embedded in vitreous ice, leads to a model for the organization of the RNAP subunits.