Influence of G-quadruplex structures on gene expression

Abstract – 

Title:

Abstract:  DNA and RNA can adopt a variety of secondary structures. Four-stranded G-quadruplex structures (G4s) form through self-recognition of guanines into stacked tetrads, and considerable biophysical and structural evidence exists for G4 formation in vitro. Their presence in cells has been demonstrated via imaging and sequencing-based methodologies.

I am interested in how G4s influence gene expression. G4s in DNA are found enriched within promoters of genes with high transcriptional activity, but the functional interaction between G4s and the process of transcription is not fully understood. I will present data showing that G4s promote transcription by augmenting polymerase occupancy at transcription start sites and counteract the influence of restrictive chromatin.

G4s also from in RNA, where I have mapped their presence using natural and artificial G4-interacting proteins. Messenger RNA coding for protein components of the ribosome are found particularly enriched in such structures, where stabilisation of G4s by small molecule ligands negatively impacts upon cellular translation. G4s are emerging as novel targets, especially in cancer, where these findings highlight further therapeutic opportunities