A molecule with a momentous effect
When two Massachusetts researchers began in the 1980s to unravel the story behind a primitive roundworm stuck in Peter Pan mode - a microscopic critter that just kept repeating the same stage of development - they had little clue they were on the cusp of something that would change biology.
But over the past decade, a series of discoveries in worms, plants, and animals have demonstrated that what seemed like a curiosity of worm biology is, in fact, the work of a whole new class of molecules with the power to turn down the effects of genes.
Now, the tiny genetic thermostats first discovered in the Peter Pan worms, molecules called microRNAs, are seen as having a crucial role to play in everything from stem cells to cancer.
"This was a form of regulation of gene expression that we simply hadn't known existed until recently, and that has the power to modify cellular processes in really quite profound ways," said David Baltimore, a Nobel laureate and professor of biology at the California Institute of Technology who works with microRNA.
"It's not a surprise that it's turned out to be so important, but it is a surprise that something as important as this was sitting out there that we didn't know about."
RNA, the lesser-known cousin of DNA, has long been considered the workhorse of the cell. RNA makes a copy of DNA, and the cell manufactures proteins according to the coded instructions in RNA. The microRNAs are very short strands that bind to another gene's RNA, to block production of proteins, which determine everything from eye color to the course of a disease.
The first microRNAs were discovered in worms by Victor R. Ambros of the University of Massachusetts Medical School at Worcester and Gary B. Ruvkun, of Massachusetts General Hospital and Harvard Medical School. Last month, they shared the Albert Lasker Award for Basic Medical Research with David C. Baulcombe of the University of Cambridge, who did his work in plants.
At the time, Ambros and Ruvkun both said they did not realize that what they were working on could have such a big impact, but an article published in the journal Nature in 1994 saw the potential for their work to be big.
"Although this could be a rare, deviant case, there is the tantalizing possibility that a new family of regulatory RNAs awaits discovery," the article's authors said.
That has been borne out today, with microRNA's popping up far beyond worm and plant labs.
"There are hundreds of labs looking at how microRNA's are influencing the biological processes they study," said David P. Bartel, who works on microRNA as a member of the Whitehead Institute for Biomedical Research in Cambridge, which is affiliated with MIT. "They might be interested in cancer and now that they know about microRNAs, they're thinking about how microRNAs might impinge on cancer."
Scientists have found more than 400 genes that code for microRNAs in people, and they are known to regulate a third of our protein-producing genes. Cancer researchers have been intrigued to find that the pattern of microRNAs produced in cancerous tissue is different than the microRNAs in normal tissue. MicroRNAs are also thought to play a role in embryonic stem cell development, helping control whether such cells renew themselves, or turn into adult cells.
Others are researching the role they play in the function of immune cells. For example, one study found that vaccines did not work in mice that lacked a particular microRNA, and disease-fighting cells did not function properly. Companies are eyeing the molecules as a way to treat diseases ranging from cancer to hepatitis C.
Still, there are frontiers to come as scientists learn more about how the microRNAs target genes and how they contribute to normal cell function as well as disease.
"I don't think we've yet viewed the full RNA world," Ruvkun said. He compares them to the stuff that makes up the majority of our universe, but that we can't see - dark matter.
"One of the ways we talk about these RNA's is that they are the dark matter of biology."
Carolyn Y. Johnson can be reached at cjohnson@globe.com. 