The structural features important for silencing target genes by an RNA-induced silencing complex are reported for the first time in two letters in the 31 March 2005 issue of Nature (Vol. 434, No. 7033, pp. 663-666, 666-670).
RNA interference, a mechanism that uses RNA to silence the expression of certain genes, is a promising tool for repressing disease-causing genes such as Huntington's. A complex composed of a short segment of RNA (called a guide molecule) and an Argonaute protein is thought to control RNA interference. The gene silencing function of the complex is accomplished by cleavage of complementary messenger RNA at a specific site, and is mediated by a conserved domain (called Piwi) of the Argonaute protein.
The structures of Argonaute proteins have been solved previously, but without the guide RNA molecule. To that end, David Barford and colleagues report the structure of a Piwi protein from Archaeoglobus fulgidus bound to a short guide molecule, similar to a small interfering RNA. In complementary work, Dinshaw Patel and colleagues solved the crystal structure of A. fulgidus Piwi protein bound to double-stranded RNA. Their findings help to elucidate the mechanism involved in identifying and binding target messenger RNAs before cleavage by the complex.
In addition, Leemor Joshua-Tor, Gregory Hannon and colleagues report in a Nature Structural & Molecular Biology article published online that recombinant Argonaute protein combined with a small interfering RNA accurately cleaves target RNAs.
David Barford (Institute of Cancer Research, London, UK)
Dinshaw Patel (Memorial Sloan-Kettering Cancer Center, New York, NY, USA)
Leemor Joshua-Tor (Cold Spring Harbor Laboratory, NY, USA)
(C) Nature press release.
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