Molecular Biology Select

One of the first activities identified in the RNA interference (RNAi) pathway was siRNA-mediated endonucleolytic cleavage of target transcripts, referred to as the “slicer” function of Argonaute proteins. This activity was later shown to be mediated by Argonaute2 (Ago2) in both flies and mammals, and to be important for RNAi responses in Drosophila to exogenous double-stranded (ds)RNAs such as those generated by viruses during infection. Whether Ago2 has an important role in endogenous gene regulation, and, indeed, whether endogenous siRNAs exist in flies and mammals and what their biological functions could be have been open questions. A series of new studies now report the existence of endogenous siRNAs in both the germline and soma of flies, and in mouse oocytes, providing important insights into the biological roles of this class of small RNAs. The two mouse studies further reveal a role for pseudogenes in gene regulation via the RNAi pathway, and provide interesting insights into the evolutionary pressure for conservation of Ago2 catalytic activity