RNA Pol II subunits in the regulation of transcription and genome instability

The RNA Pol II complex transcribes the genes that codify the proteins in our body. This is tightly controlled through interactions with transcription-regulatory factors. Although there is much research characterising the roles of these factors, very little, if anything, is known about how the multiple subunits of the RNA Pol II are important for the regulation of transcription. So far the RNA Pol II has been characterised as a whole complex of 12 proteins. However, our analysis of cancer genomic databases shows that single subunits can be upregulated and this associates with aggressive tumours and poor survival.

We hypothesise that these single upregulations deplete transcription-regulatory factors from RNA Pol II. This would lead to a defective transcription process associated with increased genome instability. We will analyse how the overexpression of single subunits affects RNA Pol II transcription, identifying which transcription processes and stages are particularly affected. We will also analyse the genome instability, identifying the sites of DNA damage and correlating them with the transcription defects identified by our parallel analysis.