RNAi dissects signal pathway

In the first published real use of high-throughput RNAi screening in a laboratory setting, a group of researchers at the University of California, San Francisco, has identified novel negative and positive regulators of a Drosophila melanogaster signal transduction pathway.

Edan Foley and Patrick O'Farrell report their study of Drosophila's innate immune defense system in the June 22 PLoS Biology. To dissect the pathway, the team created a library of 7216 double-stranded Drosophila RNAs that interfered with most of the phylogenetically conserved genes.

The authors identified numerous components of signal transduction, including negative and positive regulators of innate immune signaling, a hierarchy of gene action, and a novel gene, sickie—required for activation of a key component of the pathway, Relish.

"These double-stranded RNA messages are really powerful—and particularly powerful and easy to use in Dropsophila," O'Farrell said. "We can make any double-stranded RNA, pretty much, and we just pipette it on ...