RNA studies advance holds out hope for cancer drug development
An international research team led by our University has made a breakthrough advance that could pave a new route for the development of anti-cancer drugs.
Professor Ian Eperon and Dr Cyril Dominguez from the Institute of Structural and Chemical Biology led the team that developed a new method to analyse the RNA step in expressing our genetic code.
Dr Dominguez, of the Department of Molecular and Cell Biology, said: “Our research aims at understanding how four-stranded RNA structures called G-quadruplexes affect cellular processes such as RNA splicing. In this research, we describe a novel method that, for the first time, allows us to show that G-quadruplexes form in long RNAs and in conditions where the splicing reaction can take place.”
G-quadruplexes are specific structures formed when a piece of DNA or RNA folds into a four-stranded structure. DNA G-quadruplexes have been shown to be associated with diseases such as cancer and many small molecules called G-quadruplex binders have been developed as putative novel anti-cancer drugs, the best example being Quarfloxin that reached a phase II clinical trial.
RNA G-quadruplexes are also believed to play important roles in cancers but to date there are no straightforward methods to prove that they exist in cells. If they form and do control RNA splicing, then the design of molecules that bind them would be a new route for the development of anti-cancer drugs.
Professor Eperon said: “Our novel method, FOLDeR, will allow RNA scientists to investigate the existence of G-quadruplexes in physiological condition allowing a better understanding of their role in cellular processes. It is particularly interesting that the RNA we have been studying is one that plays an important role in some cancers. When the RNA is spliced using one set of sites, it produces a protein favouring cell survival. This is a problem for cancer treatments, many of which work by damaging growing cells in the hope that they will then die. However, when an alternative set of sites is used, the RNA produces a protein that encourages cell death. We have shown that G-quadruplexes form near the alternative sites, and our hope is that we can target these to shift splicing towards the pro-death pattern.”
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