Credit: COURTESY OF LEEMOR JOSHUA-TOR Greg Hannon's group at Cold Spring Harbor Laboratory was one of many labs scrambling to identify Slicer, the enzyme doing the cutting in RNA-mediated interference. Using biochemical mutagenesis, in vivo knockouts, and enzymatic assays, they had all but pegged Argonaute2. But, says Hannon, "We were stuck ? We could go right up to the edge of saying it was Argonaute without actually saying it." Just bef" /> Credit: COURTESY OF LEEMOR JOSHUA-TOR Greg Hannon's group at Cold Spring Harbor Laboratory was one of many labs scrambling to identify Slicer, the enzyme doing the cutting in RNA-mediated interference. Using biochemical mutagenesis, in vivo knockouts, and enzymatic assays, they had all but pegged Argonaute2. But, says Hannon, "We were stuck ? We could go right up to the edge of saying it was Argonaute without actually saying it." Just bef" />
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What Argonaute does

Credit: COURTESY OF LEEMOR JOSHUA-TOR" /> Credit: COURTESY OF LEEMOR JOSHUA-TOR Greg Hannon's group at Cold Spring Harbor Laboratory was one of many labs scrambling to identify Slicer, the enzyme doing the cutting in RNA-mediated interference. Using biochemical mutagenesis, in vivo knockouts, and enzymatic assays, they had all but pegged Argonaute2. But, says Hannon, "We were stuck ? We could go right up to the edge of saying it was Argonaute without actually saying it." Just bef

By | September 1, 2006

<figcaption> Credit: COURTESY OF LEEMOR JOSHUA-TOR</figcaption>
Credit: COURTESY OF LEEMOR JOSHUA-TOR

Greg Hannon's group at Cold Spring Harbor Laboratory was one of many labs scrambling to identify Slicer, the enzyme doing the cutting in RNA-mediated interference. Using biochemical mutagenesis, in vivo knockouts, and enzymatic assays, they had all but pegged Argonaute2. But, says Hannon, "We were stuck ? We could go right up to the edge of saying it was Argonaute without actually saying it."

Just before he accepted defeat, however, a CSHL colleague, Leemor Joshua-Tor, invited him into a darkened room and gave him a pair of 3D glasses. She'd solved the crystal structure of Argonaute, and it revealed a structural homology to RNAse H providing guidance for targeted mutagenesis. "There's just no substitute for when you see it sitting there in 3D," Hannon says. The labs published their milestone findings together in 2004.1,2 "Crystal structures are often important for establishing biological frameworks," says Tom Cech at Howard Hughes Medical Institute. "But here it really contributed to an unanticipated discovery."

So, Argonaute slices, but its tricks don't stop there. Joshua-Tor and others have been busy implicating it in chromatin remodeling, another facet of RNA mediated interference. "We've gotten to a point where nothing we do is fast enough," says Joshua-Tor. "The whole field is moving at record speed."

References

1. J. Song et al., "Crystal structure of Argonaute and its implications for RISC Slicer activity," Science, 305:1434-7, 2004. (Cited in 140 papers) 2. J. Liu et al., "Argonaute2 is the catalytic engine of mammalian RNAi," Science, 305:1437-41, 2004. (Cited in 180 papers)
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Comments

September 29, 2006

The article "What Argonaute does" provides exciting new information. The author could have however been a bit more "generous" and provided some details about what RNAse H does, without the reader having to take the extra effort google it up.

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