The breakthrough work was published online in the journal Nature on 10 October 2013.
Headed by Professor Daniel Tenen, Director of CSI Singapore, the scientists found a new noncoding ribonucleic acid (RNA) that offers the potential for “switching on” tumour suppressors which have been shut off. This novel RNA belongs to a RNA class that is critical in regulating DNA methylation, a process in which certain building blocks of the DNA are chemically modified without resulting in a change in the code itself.
DNA methylation is associated with the silencing of gene expression and is found in many diseases. For instance, in cancer, genes called tumour suppressors that inhibit tumour formation are often silenced or shut off in the cancer cells.
The scientists focused on a noncoding RNA regulating a specific tumour suppressor, known as CEBPA. The silencing of CEPBA is linked to Acute Myeloid Leukaemia, lung cancer and other types of cancer. The team demonstrated that the noncoding RNA binds to an enzyme essential for DNA methylation and prevents this process from happening in the CEBPA gene. This principle, which is likely to extend to thousands of other genes, can potentially be used to “switch on” tumour suppressors that have been shut off.
Prof Tenen said: “We started out studying a basic scientific question, namely what was the noncoding RNA doing, simply to satisfy our scientific curiosity. In the process, we discovered the novel finding that RNA inhibits methylation and experimentally we can introduce RNAs to ‘switch on’ tumour suppressors which have been shut off. Our results suggest strategies for gene-selective demethylation of therapeutic targets in human diseases such as cancer.”
The researchers will be looking into developing tools for targeted activation of other tumour suppressors, as well as examining the role of RNA in regulating other epigenetic marks.
National University of Singapore.