Argonaute and Trimmer generate Dicer-independent priRNAs and nucleate RNAi. Schizosaccharomyces pombe

RNA interference is involved in silencing of transposable and repetitive elements. How these elements are initially recognized by RNAi is a fundamental and unanswered question. We previously identified a class of Dicer-independent small RNAs, called primal small RNAs (priRNAs), in fission yeast. The mechanism by which Dicer-independent small RNAs are generated is not clear for any species. Here we reconstitute priRNA biogenesis in vitro and demonstrate that priRNAs can nucleate RNAi in vivo. We identify 3'-5' exonuclease Trimmer and show that Argonaute, loaded with longer RNA precursors, recruits Trimmer to generate the new 3' end. Next, we show that antisense priRNAs accumulate in rrp6Δ cells and nucleate RNAi at subset of protein coding genes in a Trimmer- and priRNA-dependent manner. Thus, Rrp6-mediated degradation of antisense transcripts and priRNA precursors protects the genome from spurious RNAi. Our results suggest that Argonaute association with random RNA degradation products triggers RNAi in a process of transcriptome surveillance. Overall design: small RNA profiling in wild type S. pombe cells and in mutant cells