WE KNOW they are vital for growth and development in plants and worms, and now it seems that small pieces of RNA called microRNAs also play a key role in mammals. They might even point the way to new treatments for diabetes.
The conventional view is that the main function of RNA is to convey instructions from DNA to the protein-making factories in cells – a task carried out by large molecules of “messenger” RNA. But researchers recently discovered that short pieces of RNA called microRNAs can control the production of specific proteins by targeting their messenger RNA. MicroRNAs have been shown to be important in plants and nematode worms. But what about mammals? Markus Stoffel’s team at The Rockefeller University in New York has now discovered a microRNA that helps control insulin secretion in mice.
After studying 67 microRNAs extracted from insulin-producing cells in the islet cells of the pancreas, his team identified one called miR-375 that blocks secretion of insulin, the hormone that regulates blood glucose levels. What’s more, blocking miR-375 increases insulin secretion. The team went on to show that miR-375 reduces secretion by interfering with the messenger RNA for myotrophin, a protein that “packages” insulin prior to its release into the bloodstream (Nature, vol 432, p 226).
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Stoffel has shown that diabetic animals make too much miR-375. A drug that blocks miR-375 and so allows more insulin to be secreted could help treat certain forms of diabetes, he says. “If you can inhibit miR-375, you could potentially increase insulin production.” And since miR-375 is produced only by islet cells, such a drug should have few side effects.
Stoffel says that the best bet is to block miR-375 with “antisense” strands of RNA, whose sequence is complementary to that of the microRNA. These would bind to and neutralise miR-375 exclusively. The snag would be making sure enough antisense strands get into pancreatic cells to make a difference. But Stoffel is confident the problem can be solved. “I think the technology will be available to deliver specific antisense RNAs to patients,” he says.