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.