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A team of Howard Hughes Medical Institute (HHMI) scientists has peeled back some of the mystery of how cells are able to turn off genes selectively to control critical events of development. The new insights arise from the first clear molecular images of the structure of Dicer, an enzyme that enables cells to dissect genetic material precisely.

The finding, which is reported in the January 13, 2005, issue of the journal Science by an HHMI research team at the University of California, Berkeley, provides scientists with new information about a mechanism that enables cells to silence genes, a process that governs key developmental events ranging from brain development to stem cell differentiation.

The study was led by Jennifer A. Doudna, a Howard Hughes Medical Institute investigator at the University of California, Berkeley. Doudna's research team used x-ray crystallography to assemble a detailed three-dimensional picture of an enzyme known as Dicer. In cells, Dicer jumpstarts RNA interference, a process that causes genes to be turned off and which, in turn, prompts a host of key developmental events.

With the structure of Dicer solved, Doudna's group showed that the enzyme is more than a molecular cleaver -- it also carefully measures and snips strands of RNA into precise increments. When Dicer cleaves large strands of RNA into smaller fragments, it initiates the process of RNA interference, which can turn genes off and thereby dictate key developmental events.

"The bottom line we've learned from the structure is that Dicer is a molecular ruler," Doudna explained. "It gives us a lot of insight into how the mechanism works."

Dicer, which is ubiquitous in the cells of higher animals, including humans, is a widely studied molecule. It was first discovered in 2001 by Gregory J. Hannon, an HHMI investigator at Cold Spring Harbor Laboratory, and has become a powerful laboratory tool to study cancer and other developmental events thr
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Source:University of Pittsburgh Medical Center


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