Targeting Argonaute to chromatin

In many eukaryotes, siRNAs bound to Argonaute proteins guide chromatin-modifying enzymes to complementary loci, resulting in transcriptional gene silencing. Multiple lines of evidence indicate that siRNAs base-pair with longer RNAs produced at target loci, but the possibility that siRNAs base-pair directly with DNA remains an attractive hypothesis. In a recent study, Shimada et al. (pp. 2571-2580) conducted experiments that address these alternative hypotheses, yielding additional evidence that fission yeast siRNA-Argonaute silencing complexes are recruited to target loci exclusively via interactions with nascent transcripts.