Scientists have gotten their first detailed look at the molecular structure of an enzyme that Nature has been using for eons to help silence unwanted genetic messages. A team of researchers with Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California at Berkeley used x-ray crystallography at Berkeley Lab’s Advanced Light Source (ALS) to determine the crystal structure of Dicer, an enzyme that plays a critical role in the process known as RNA interference. The Dicer enzyme is able to snip a double-stranded form of RNA into segments that can attach themselves to genes and block their activity.
A front-on view of a ribbon representation of Dicer shows the enzyme to resemble 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. A segment of double-stranded RNA (blue) is shown passing through the Dicer enzyme.
“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,” said Jennifer Doudna, a biochemist who led this study. Doudna, a leading authority on RNA molecular structures, holds joint appointments with Berkeley Lab’s Physical Biosciences Division, UC Berkeley’s Department of Molecular and Cell Biology and Department of Chemistry. She’s also an investigator with the Howard Hughes Medical Institute (HHMI).
“Knowing the structure of Dicer sets the stage for understanding how Dicer enzymes are involved in other phases of the RNA interference pathway,” Doudna said. “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.”
Lynn Yarris | EurekAlert!
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