The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs

In contrast to microRNAs and Piwi- associated RNAs, short interfering RNAs ( siRNAs) are seemingly dispensable for host- directed gene regulation in Drosophila. This notion is based on the fact that mutants lacking the core siRNA- generating enzyme Dicer- 2 or the predominant siRNA effector Argonaute 2 are viable, fertile and of relatively normal morphology(1,2). Moreover, endogenous Drosophila siRNAs have not yet been identified. Here we report that siRNAs derived from long hairpin RNA genes ( hpRNAs) programme Slicer complexes that can repress endogenous target transcripts. The Drosophila hpRNA pathway is a hybrid mechanism that combines canonical RNA interference factors ( Dicer- 2, Hen1 ( known as CG12367) and Argonaute 2) with a canonical microRNA factor ( Loquacious) to generate similar to 21- nucleotide siRNAs. These novel regulatory RNAs reveal unexpected complexity in the sorting of small RNAs, and open a window onto the biological usage of endogenous RNA interference in Drosophila.