Structural and dynamic consequences of inosine, 2′-O-methylation, and N6-methyladenosine modifications in RNA G-quadruplex: A molecular dynamics study

RNA G-quadruplexes (rG4) are stable non-canonical structures, often found to regulate important biological processes such as transcription, translation, splicing, RNA localization, and other steps in gene expression. rG4 structures can also influence DNA-related processes e.g. DNA replication, telomere elongation and homeostasis, and recombination. Due to the involvement of rG4s in such important processes, these structures are potential therapeutic targets against different diseases e.g., viral infection and cancer. Hence, a better understanding of the structure and stability of rG4s and their role in various therapeutically important cellular processes can help in the design of effective therapeutic strategies for targeting such structures. In the present study, we present our findings on the structural and dynamic effect of RNA modifications (inosine; 2′-O-methylation, and m 6 A-methylation) on RNA G-quadruplex structure from molecular dynamics simulations. Additionally, we also report the dynamic and energetic aspects of inter-quadruplex interactions and the influence of non-G purine tetrads neighboring the inter-quadruplex junction on the interactions.