Short argonaute RNA guides diversity

Two prokaryotic defence systems, Argonautes (pAgos) and CRISPR-Cas, detect invader nucleic acids using complementary guides. Upon recognition, the target is cleaved through nuclease activities of pAgo or Cas proteins, protecting the cell from invasion. However, not all pAgos are active nucleases. Members of a large clade of short pAgos bind nucleic acid guides but lack nuclease activity suggesting a different mechanism of action. Here, we have investigated short pAgos associated with a putative effector nuclease, NbaAgo from Novosphingopyxis baekryungensis and CmeAgo from Cupriavidus metallidurans. We have shown that these pAgos form a heterodimeric complex, SPARDA, with co-encoded effector proteins. RNA-guided target DNA recognition unleashes the nuclease activity of SPARDA leading to indiscriminate collateral cleavage of DNA and RNA. Activation of SPARDA by plasmids or phages results in degradation of cellular DNA and cell death or dormancy, thus protecting bacterial population from invaders. The collateral activity of SPARDA allows highly sensitive detection of specific DNA targets. SPARDA expands the list of prokaryotic immune systems that elicit suicidal cell response with a unique range of nuclease activities, creating additional opportunities for biotechnologies.