Two prokaryotic defence systems, prokaryotic Argonautes (pAgos) and CRISPR–Cas, detect and cleave invader nucleic acids using complementary guides and the nuclease activities of pAgo or Cas proteins. However, not all pAgos are active nucleases. A large clade of short pAgos bind nucleic acid guides but lack nuclease activity, suggesting a different mechanism of action. Here we investigate short pAgos associated with a putative effector nuclease, NbaAgo from Novosphingopyxis baekryungensis and CmeAgo from Cupriavidus metallidurans. We show that these pAgos form a heterodimeric complex with co-encoded effector nucleases (short prokaryotic Argonaute, DNase and RNase associated (SPARDA)). 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, conferring target-specific population protection and expanding the range of known prokaryotic immune systems.

两种原核防御系统，原核 Argonautes (pAgos) 和 CRISPR-Cas，利用互补引导和 pAgo 或 Cas 蛋白的核酸酶活性来检测和切割入侵者核酸。然而，并非所有 pAgo 都是活性核酸酶。一大群短 pAgos 结合核酸向导，但缺乏核酸酶活性，表明不同的作用机制。在这里，我们研究了与假定的效应核酸酶相关的短pAgo，即来自Novosphingopyxis baekryungensis的NbaAgo和来自Cupriavidus metallidurans的CmeAgo 。我们证明这些 pAgos 与共同编码的效应核酸酶（短原核 Argonaute、DNase 和 RNase 相关 (SPARDA)）形成异二聚体复合物。 RNA 引导的目标 DNA 识别释放 SPARDA 的核酸酶活性，导致 DNA 和 RNA 的不加区别的附带切割。质粒或噬菌体激活 SPARDA 会导致细胞 DNA 降解和细胞死亡或休眠，从而赋予目标特异性群体保护并扩大已知原核免疫系统的范围。