Many genes identified as targets of RNA interference (RNAi) in the fruitfly Drosophila could be false, suggests a paper published online by Nature.
During RNAi, short fragments of RNA bind to complementary sequences in the messenger RNA produced by a target gene, effectively silencing expression of that gene. Some studies have suggested that these small RNAs can each have hundreds of target genes in a genome.
Philip Beachy and his colleagues say that many proposed targets of RNAi screens could be artefacts. The team searched for new members of the well-studied Wingless signalling pathway by inserting multiple interfering RNAs into Drosophila cells. They found that the RNAs displayed significant off-target effects: the majority of targets are false positives resulting from interactions between three-letter repeats present in these target genes and the interfering RNAs, and from indirect effects on known Wingless pathway components. The authors suggest several measures to produce more reliable lists of genes targeted by RNAi.
Philip A Beachy (Stanford University, CA, USA)
(C) Nature press release.
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