Monitoring messenger RNA stability could be used to screen for cancer treatments, say researchers in Switzerland.

Messenger RNA (mRNA) molecules are working copies of genes that direct the synthesis of proteins. Cells can control the amounts of proteins they produce by changing the stability of the mRNA molecules involved. Now, Christoph Moroni and colleagues at the Institute for Medical Microbiology, in Basel, have found a way to monitor changes in mRNA stability simply and quickly.

Cells expressing green fluorescent protein

Moroni's method uses mRNAs engineered to include a green fluorescent protein next to regions that are rich in adenine and uracil (AREs). Relatively unstable mRNAs contain AREs and Moroni found that the mRNAs lasted longer and gave a stronger fluorescence when these regions were deleted. He observed a similar strong fluorescence when mRNA-stabilising compounds were added, providing a way to screen compounds that alter mRNA stability.

Moroni used his method to find that some cancer cells have a defect in mRNA decay, causing elevated mRNA and protein levels. mRNAs have a turnover, explained Moroni, they are 'born' by transcription and 'die' by enzymatic degradation. mRNA levels in cells are set by the difference between these processes. Understanding the mechanisms behind this control not only 'provides insight into how normal cells are activated to do their normal job, but also how these mechanisms, when uncontrolled, may lead to disease,' said Moroni. 

The method could help scientists understand how particular anticancer drugs work, added Moroni, and provide a way of screening compound libraries for new drugs. One advantage of the system is its simplicity, he said, rendering the system 'amenable to automation for high throughput screening.'

'A great number of genes associated with growth processes, including cancer biology and inflammatory processes, are regulated at the level of mRNA turnover,' said David Port, an expert in mRNA stability at the University of Colorado, US. 'These methods may provide an essential breakthrough to more rapidly detect the biological impact of pharmacological or genetic interventions.'

Michael Smith