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Scientists have taken their first detailed look at the molecular structure of an ancient gene-silence enzyme. Jennifer Doudna of the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California at Berkeley and colleagues obtained an X-ray crystallography of "Dicer", an enzyme that chops RNA into segments capable of switching off genes. This process of RNA interference, which was discovered only as recently as 1998, is an ancient gene-silencing process that plays a fundamental role in a number of important functions, including viral defense, chromatin remodelling, genome rearrangement, developmental timing, brain morphogenesis and stem cell maintenance; all hinging on the activity of Dicer. "With this crystal structure, we've learned that Dicer serves as a molecular ruler, with a clamp at one end and a cleaver at the other end a set distance away, that produces RNA fragments of an ideal size for gene-silencing," explains Doudna. The Advanced Light Source at Berkeley was key to the crystal structure determination, she adds. The front-on view it produced reveals an enzyme resembling an axe with the RNA clamp at the handle (the PAZ domain) and the cleaver at the blade (RNase IIIa and IIIb). A flat connector area measuring 65 angstroms is the ruler portion that is used to measure out segments of 25 nucleotides (bases) in length. "Knowing the structure of Dicer sets the stage for understanding how Dicer enzymes are involved in other phases of the RNA interference pathway," Doudna explains, "In human cells, the evidence points to Dicer being part of a larger molecular complex that directs the RNA interference process. The core structure of Dicer has been highly conserved by evolution and could serve as a guide in redesigning the RNA molecules that direct specific gene-silencing pathways." Related links:
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Dicey enzyme structure revealed |
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