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Berkeley scientists get first detailed look at Dicer

e activities depend upon Dicer, so understanding this enzyme's molecular structure is a critical step.

The results of this research are reported in the January 13, 2006 edition of the journal Science in a paper entitled: Structural Basis for Double-Stranded RNA Processing by Dicer. Co-authoring the paper with Doudna were Ian MacRae, Kaihong Zhou, Fei Li, Adrian Repic, Angela Brooks, Zacheus Cande and Paul Adams.

RNA - ribonucleic acid has long been known as a multipurpose biological workhorse, responsible for carrying DNA's genetic messages out from the nucleus of a living cell and using those messages to make specific proteins in a cell's cytoplasm. In 1998, however, scientists discovered that RNA can also block the synthesis of proteins from some of those genetic messages. This gene-silencing process is called RNA interference and it starts when a double-stranded segment of RNA encounters the enzyme Dicer. Double-stranded RNA (dsRNA) is formed from two single strands of RNA with complementary base sequences.

Dicer cleaves dsRNA into smaller fragments called short interfering RNAs (siRNAs) and microRNAs (miRNAs). Dicer then helps load these siRNA and miRNA fragments into a large multiprotein complex called RISC, for RNA-Induced Silencing Complex. RISC can seek out and capture messenger RNA (mRNA) molecules (the RNA that encodes the message of a gene) with a base sequence complementary to that of its siRNA or miRNA. This serves to either destroy the genetic message carried by the mRNA outright, or else block the subsequent synthesis of a protein.

Until now, it has not been known how Dicer is able to recognize dsRNA and cleave those molecules into products with lengths that are exactly what is needed to silence specific genes. Doudna and her co-authors were able to purify and crystallize a Dicer enzyme from Giardia intestinalis, a one-celled microscopic parasite that can infect the intestines of humans and animals. This
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
12-Jan-2006


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