The findings built on work over the past decade in roundworm mutants with striking developmental defects. In 1991, Lee and Ambros found lin-4, a surprisingly small gene that produced a particular hook-shaped RNA. This little gene seemed to be a temporal switch in development, but unlike most timing controls, instead of synthesizing protein, it repressed protein production from certain other genes.
Lin-4 was the first gene of its kind identified, but was an only example in just one organism. "So initially, we worked on something novel, a gene important for C. elegans development, but whether or not it was important for other animals, let alone medical science, was in doubt," Ambros recalled. Things moved forward after a second, different small RNA also identified in the roundworm was found throughout the evolutionary treefrom sea urchins to insects and mice, to humans.
Several of the small RNAs identified in the current work are also evolutionarily ancient. Among these is mir-1, found in worms, flies and humans, which appears relatively specific to heart tissue. Ambros speculates that mir-1 may play a role in heart development and holds importance in some diseases of the heart.
The next step is to identify all the new RNAs and determine how they function. Roundworms alone contain at least 100, Ambros estimates conservatively. "The nice thing about uncovering this many microRNAs is that it places before us a buffet of questions and research projects larger than any one group could possibly pursue."
The excitement lies in these unanswered questions and new opportunities. The convergence of researchers in different disciplines sparks unanticipated
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Contact: Hali Wickner
hali.wickner@dartmouth.edu
603-650-1520
Dartmouth Medical School
25-Oct-2001