Reaping the rewards of RNAi

Loss-of-function phenotype analysis in nematode worms has benefited tremendously from a well-annotated genome and the efficacy of RNAi gene-inactivation technology. In the January 16 Nature, Ravi Kamath and colleagues report the results of the first genome-wide RNAi screen in Caenorhabditis elegans (Nature, 421:231-237, January 16, 2003).

Worms were fed on bacteria expressing double-stranded RNA for each C. elegans target gene. A library of 16,757 bacterial strains — covering 87% of predicted genes — was screened for genes implicated in sterility, embryonic lethality, slow growth or post-embryonic defects. About 10% of strains gave clear mutant phenotypes. The most common RNAi phenotype is embryonic lethality.

Worm genes with orthologues in other species were more likely to have a detectable RNAi phenotype than other genes, and genes that exist as a single copy were 2-3 times more likely to have a phenotype. Some protein domains showed association with particular types of RNAi phenotypes. ...