Dynamic G-Quadruplexes in the Rous Sarcoma Virus Genome: Scaffolds for Protein Interaction and Potential Anti-Viral Targets.

The Rous sarcoma virus (RSV) is an onco-retrovirus that infects avian species such as the chicken (Gallus gallus). RSV is the first oncovirus to be described, and the oncogenic activity of this virus is related to the expression of a tyrosine kinase that induces carcinogenic transformation. Interestingly, we have noted that the RSV genome contains various potential G4-forming sequences. Among these, two sequences in the GAG and POL genes show high G4-forming potential. Additionally, the SRC oncogene also harbours a putative G4 forming sequence. In this study, we have characterised the G4 formation and topology in these three loci in the RSV-DNA. We have found that these sequences form dynamic G4 structures in physiological conditions, and such dynamicity may be associated with their cellular functions. Further, we have also established that these G4s are recognised by G4 interacting small-molecule ligands and the G4-stabilising protein nucleolin. The binding of these ligands induces structural shifts in the G4s, leading to changes in structure and stability. Thus, the RSV-DNA G4s may be further studied as targets to control its infection and oncogenic effects.