RNA 'switch' could turn off cancer
could switch off cancer tumours, preventing them from growing.
Dr Alexandre Akoulitchev, from the University of Oxford, discovered a piece of RNA that inhibits a key gene in tumour growth, dihydrofolate reductase (DHFR). This gene produces a protein that helps control folate levels in the body, a chemical that tumour cells need to divide rapidly.
The discovery of such an important role for a molecule previously seen as scrap opens up a myriad of possible new RNA therapeutics, and not only for cancer.
The Human Genome Project identified about 34,000 genes responsible for producing proteins. The remaining part of the genome - in fact most of it - was considered to be 'junk' DNA with no function.
RNA acts as a mediator between the DNA of our genes and the proteins they ultimately produce when activated. Although scientists have known for some time that not all RNA was directly involved in protein synthesis, latest estimates suggest that this 'junk' DNA actually produces around half a million varieties of RNA of unknown function.
"There has been a quiet revolution taking place in biology during the past few years over the role of RNA," says Dr Akoulitchev.
"Scientists have begun to see 'junk' DNA as having a very important function. The variety of RNA types produced from this 'junk' is staggering and the functional implications are huge," he continued.
Dr Akoulitchev found that the DHFR gene contained two promoters, a major promoter that produces messenger RNA (mRNA), which then produces DHFR. The minor promoter produces non-coding RNA (ncRNA). Dr Akoulitchev explained to DrugResearcher.com that the ncRNA binds to a transcription protein and effectively knocks the complex off the DNA and switches the gene off.
Despite the fact that these same transcription factors assemble on all genes, the ncRNA only interferes with the DHFR gene thanks to its specific triple-helix structure.
"Inhibiting the DHFR gene could help prevent the growth of neoplastic cancerous cells, ordinary cells which develop into tumour cells, such as prostate cancer cells," explained Dr Akoulitchev.
"In fact, the first anti-cancer drug, Methotrexate, acts by binding and inhibiting the enzyme produced by this gene."
He added: "Here, we control the master switch rather than the enzyme."
Dr Akoulitchev explained that this is just one good example of how important RNA could be. With more research and a better understanding of other pieces of scrap RNA, this mechanism of switching off genes could be exploited in other genes and have important implications in developing other therapies.
