No more than five years ago, microRNAs were considered to be little more than light seasoning in the genetic soup, distant and unnecessary cousins to the main ingredients, DNA, which contains all the genetic instructions for the human body, and RNA, which translates DNA's message into proteins - the building blocks of life.
Scientists now think the pint-sized pieces of RNA may control as much as one-third of human gene expression by seeking out and binding to messenger RNA, thereby adjusting the protein-manufacturing process.
But for microRNAs to do their jobs, scientists believe an enzyme called Dicer must be present. Harfe, who worked in collaboration with researchers at the University of California at San Francisco and the Harvard Medical School, genetically modified mice so that scientists could eliminate Dicer in specific tissues at any stage in the developmental process, thus opening a window into the role of microRNAs in limb development.
In cases where Dicer is not present in developing limb tissue, Harfe showed that microRNAs were not processed and limbs were visibly smaller.
"Many of the birth defects we see in people are mimicked by the defects we've seen in this mouse model," said Xin Sun, Ph.D., an assistant professor of genetics at the University of Wisconsin who is familiar with the research but who did not participate in it. "It indicates mutations in microRNAs might be responsible for birth defects, and this has not been discovered before. Using this same approach, we can look at other embryonic organs and ask what microRNAs do as a group."
Other research indicates microRNAs may play a role in diseases ranging from cancer to AIDS.
"There is indirect evidence that if you remove two microRNAs from the human genome, leukemia develops," Harfe said. "We envision our mouse model may be a tool to directly test how microRNAs are involved in human cancers."