“This paper expanded the realm of small RNAs by adding a previously unknown class that act mainly in the germline and which are likely required for proper gametogenesis.”

The Argonaute proteins bind to small RNAs and use these as guides to silencing of target genes. One group of Argonautes bind to microRNAs and siRNAs, and their functions are relatively well established. However, at the time that this paper was published, the binding partners of a second group of Argonautes, the Piwi proteins, were unknown. This paper reported the identification of Piwi binding partners, the piRNAs, which also represented a new class of small RNAs.

In retrospect, this paper contributed to the process of understanding the biology of Piwi proteins, ultimately leading, through the work of several investigators in the field, to a picture where piRNAs act in the defense of the genome against parasitic nucleic acids, namely transposons. Ironically, the piRNAs that were described in this manuscript are probably expressed too late to act explicitly in that process, and thus this particular group of piRNAs remain mysterious.

Over the past few years, we have been consistently surprised by the many roles that small RNAs play in eukaryotic biology. This paper expanded the realm of small RNAs by adding a previously unknown class that act mainly in the germline and which are likely required for proper gametogenesis.

This work was a logical outgrowth of our many years of work on the biology of the other clade of Argonaute proteins—those that act in concert with microRNAs and siRNAs. As our understanding of those proteins increased, it only served to highlight our ignorance concerning the Piwi clade.