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Twin molecular scissors link creation of microRNAs with gene-silencing

(Philadelphia) One of the body's primary strategies for regulating its genome is a kind of targeted gene silencing orchestrated by small molecules called microRNAs, or miRNAs. First observed only a few years ago, these molecules appear to inactivate messenger RNA, itself responsible for translating genes into proteins. Scientists have been eager to know more about miRNAs, clearly important players on the genetic field despite having gone unnoticed for so long. How are they produced? And how do they work?

In a series of studies published over the past year, a research team at The Wistar Institute has provided considerable insight into the world of miRNAs. In their first study, which appeared last year in Nature, they identified a two-protein complex, called the microprocessor, which controls the earliest steps in the creation of miRNAs in the cell nucleus. In their next study, published in Nature earlier this year, the Wistar group described a three-protein complex that picks up the process in the cell cytoplasm and carries it through to the maturation of the finished miRNAs.

Now, in new findings published online November 3 in Cell, Wistar professor Ramin Shiekhattar, Ph.D., and his colleagues report that the three-protein complex has been identified as RISC, a previously glimpsed but ill-defined molecular complex known to be involved in gene silencing. RISC, the new study demonstrates, not only oversees production of miRNAs, as described in the earlier study this year, but is also responsible for miRNA specificity in silencing particular messenger RNAs.

In RISC, two of the three components, Dicer and Argonaute 2, are enzymes bound together by the third member, TRBP. Dicer cuts double-stranded precursor molecules shaped like hairpins into pairs of short single-stranded miRNAs in essence, nipping off the bend in the pin. RISC then unzips the two single-stranded miRNAs from each other and identifies and holds one as a guide to help it find the
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Contact: Franklin Hoke
hoke@wistar.org
215-898-3716
The Wistar Institute
3-Nov-2005


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