Somatic piRNA biogenesis.

Piwi-interacting RNAs (piRNAs) protect animal germ cells from transposons and other selfish genetic elements. Of the three types of animal small-silencing RNAs—smallinterfering RNAs (siRNAs), microRNAs (miRNAs), and piRNAs—piRNAs are the least well understood, because we lack good tools for studying how they are made and how they function. Brennecke et al have now established a method for triggering RNA interference (RNAi) solely in Drosophila follicle cells, a specialized somatic cell that abuts the developing oocyte and which expresses a simplified version of the piRNA pathway present in animal germ cells. Their initial results already suggest a revision for our model of the piRNA pathway, and promise to accelerate the study of this enigmatic small RNA class. Transposons and repetitive sequences compose nearly half the human genome and about a third of the genome of flies. Although some transposons are ancient relics that have lost the ability to jump to new locations, others remain active, poised to cause mischief. piRNAs (originally called rasiRNAs) protect animal germ cells from these genetic parasites by preventing transposons from producing the proteins required for them to transpose. Thus, piRNAs ensure the genomic integrity of eggs and sperm, protecting the germ cell DNA from the double-stranded breaks and insertional mutagenesis caused by active transposons. piRNAs are one of three types of ‘small-silencing RNAs’ found in animals (Ghildiyal and Zamore, 2009). Small-silencing RNAs serve as guides for Argonaute proteins, specialized RNA-binding proteins that tightly bind the small RNA guide while allowing it to base pair with and dissociate from its regulatory target RNAs. The most well-studied small-silencing RNAs are siRNAs, which serve as guides for the RNAi pathway. Many readers of this journal routinely use siRNAs to reduce the expression of the genes they study. Most animals (but perhaps not mammals) produce siRNAs to defend against viruses and somatic transposons; many (including mammals) produce endogenous siRNAs to regulate genes. A second class of small-silencing RNAs, miRNAs, selectively reduce the stability and rate of translation of mRNAs with which they can partially base pair (Bartel, 2009). Both siRNAs and miRNAs derive from longer, double-stranded RNA precursors that are diced into 21–23 nt double-stranded small RNAs. Not so for piRNAs. piRNAs derive from long, single-stranded RNAs, nearly all of which are shockingly long and transcribed from genomic ‘clusters’—transposon-rich regions of the genome thought to record the waves of transposon invasions survived by an animal