Bacterial abortive-infection systems limit the spread of foreign invaders by shutting down or killing infected cells before the invaders can replicate^1,2. Several RNA-targeting CRISPR–Cas systems (that is, types III and VI) cause abortive-infection phenotypes by activating indiscriminate nucleases^3,4,5. However, a CRISPR-mediated abortive mechanism that leverages indiscriminate DNase activity of an RNA-guided single-effector nuclease has yet to be observed. Here we report that RNA targeting by the type V single-effector nuclease Cas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA (dsDNA). After recognizing an RNA target with an activating protospacer-flanking sequence, Cas12a2 efficiently degrades single-stranded RNA (ssRNA), single-stranded DNA (ssDNA) and dsDNA. Within cells, the activation of Cas12a2 induces an SOS DNA-damage response and impairs growth, preventing the dissemination of the invader. Finally, we harnessed the collateral activity of Cas12a2 for direct RNA detection, demonstrating that Cas12a2 can be repurposed as an RNA-guided RNA-targeting tool. These findings expand the known defensive abilities of CRISPR–Cas systems and create additional opportunities for CRISPR technologies.

细菌流产感染系统通过在入侵者复制^1,2之前关闭或杀死受感染的细胞来限制外来入侵者的传播。几种靶向 RNA 的 CRISPR-Cas 系统（即 III 型和 VI 型）通过激活不加选择的核酸酶^{3,4,5引起流产感染表型}. 然而，尚未观察到利用 RNA 引导的单效应核酸酶的不加选择的 DNase 活性的 CRISPR 介导的流产机制。在这里，我们报告 V 型单效应核酸酶 Cas12a2 靶向 RNA 通过双链 DNA (dsDNA) 的非特异性切割驱动流产感染。在识别具有激活原型间隔子侧翼序列的 RNA 靶标后，Cas12a2 可有效降解单链 RNA (ssRNA)、单链 DNA (ssDNA) 和 dsDNA。在细胞内，Cas12a2 的激活会诱导 SOS DNA 损伤反应并损害生长，从而阻止入侵者的传播。最后，我们利用 Cas12a2 的附带活性进行直接 RNA 检测，证明 Cas12a2 可以重新用作 RNA 引导的 RNA 靶向工具。