Tuesday, November 24, 2009
Nogales Lab Research
Transcription by RNA polymerase II (RNAPII) is a central process in eukaryotic gene regulation. While
atomic details exist for the yeast RNAPII, characterization of the human complex lags behind, mostly due
to the inability to obtain large quantities of purified material. Although the complexes have the same
protein composition and high sequence similarity, understanding of transcription and of
transcription-coupled DNA repair (TCR) in humans will require the use of human proteins in structural
studies. We have used cryo-electron microscopy, image reconstruction, and variance analysis to
characterize the structure and dynamics of human RNAPII (hRNAPII). Our studies show that hRNAPII in
solution parallels the conformational flexibility of the yeast structures crystallized in different
states, but also illustrates a more extensive conformational flexibility with potential biological
significance (Kostek et al, Structure
2006). This hRNAPII study will serve as a structural platform to build up higher order
transcription and TCR complexes and to gain information that may be unique to the human RNAPII
system.