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In 2003 we celebrated the 50th birthday of modern molecular biology. It was a half century ago that James Watson and Francis Crick discovered the structure of DNA--the stuff that genes are made of. But as the world looked back on that towering achievement, many scientists were busy looking forward, focusing their energies on RNA, a molecule that DNA needs to carry out its instructions. The excitement centers specifically on tiny RNA molecules called microRNAs. Discovered only a decade ago, these genetic wisps now appear to play a major role in the growth and development of all living things. The discovery of microRNA gives scientists a powerful new tool--and it could transform the prevention and treatment of disease.
The basic workings of DNA and RNA are no mystery. It's now well known that DNA consists of four nucleotide "bases" (A, T, C and G), whose linear sequences (AATAGGCTCC...) encode hereditary information. Genes--discrete segments of long DNA molecules--transcribe their sequences onto single-strand messenger RNA molecules, which then serve as templates for proteins. In short, DNA makes messenger RNA, and messenger RNA makes proteins. The production of a particular protein is the goal of each gene. This 50-year-old insight is the bedrock of modern biology, but science has not fully solved a related mystery. If every cell in an organism contains the same full complement of genes, why are the cells themselves so varied? How do different genes get turned on ("expressed") or off ("silenced") in just the right combinations to produce heart cells, bone cells and brain cells?
That's where microRNA enters the picture. In the early 1990s, researchers studying a species of worm discovered genes for a very short and very unusual piece of RNA. Instead of synthesizing proteins, this tiny RNA molecule latched onto messenger RNAs (chart), causing their destruction. Without messenger RNA, no protein was produced. In effect, the gene for that protein had been silenced. The discovery was initially dismissed as an oddity in a worm, but scientists have since found genes for hundreds of microRNAs in various plants and animals--200 in humans alone. Many of these genes have survived in identical forms in different species, indicating that they are essential to life. What, exactly, is their role? We now suspect that by silencing particular genes at just the right times--a process called RNA interference--they push genetically identical cells down different paths of development, enabling some to digest food while others perceive light.
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RNA interference gives researchers a new tool for understanding how living things grow--how a plant assumes a particular shape, for example, or how a baby's hand forms during gestation. Moreover, because microRNAs are so small and simple in structure, they can be manufactured for use as research tools. If scientists suspect that a particular gene is responsible for a disease, they can design microRNA to silence the gene in affected laboratory animals. If the disease is prevented or cured, the gene becomes a target for treatment.
RNA interference has yet to generate new medicines, but if the technique fulfills its promise, it could help us treat everything from viral infections to cancer. MicroRNAs could be used to seal off human cells from disease-causing viruses, or to disable viruses that gain entry. In a recent test-tube study, researchers showed that RNA interference could make cells impermeable to HIV. Early studies suggest that microRNAs can also boost the production of stem cells in culture. By blocking production of growth-promoting proteins, microRNAs may even help contain cancer cells.
It is one thing to manipulate cells in a test tube, quite another to treat people. Getting microRNAs safely into the right cells in the body will be complicated. No one has yet attempted a human experiment. Even so, a field that was just a curiosity in 1993 is now poised to change the world--all because we invested in basic research. The scientists who discovered microRNAs were not trying to prevent AIDS, grow stem cells or treat cancer. They just wanted to figure out how something happened in a worm. As Buckminster Fuller observed, "Development is programmable; discovery is not."
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