小柯机器人

德国维尔茨堡大学Chase L. Beisel等研究人员合作发现，Cas12a2通过RNA触发的dsDNA破坏引起中止性感染。该研究于2023年1月4日在线发表于国际一流学术期刊《自然》。

Title: Cas12a2 elicits abortive infection through RNA-triggered destruction of dsDNA

Author: Dmytrenko, Oleg, Neumann, Gina C., Hallmark, Thomson, Keiser, Dylan J., Crowley, Valerie M., Vialetto, Elena, Mougiakos, Ioannis, Wandera, Katharina G., Domgaard, Hannah, Weber, Johannes, Gaudin, Thomas, Metcalf, Josie, Gray, Benjamin N., Begemann, Matthew B., Jackson, Ryan N., Beisel, Chase L.

Issue&Volume: 2023-01-04

Abstract: Bacterial abortive-infection systems limit the spread of foreign invaders by shutting down or killing infected cells before the invaders can replicate1,2. Several RNA-targeting CRISPR–Cas systems (that is, types III and VI) cause abortive-infection phenotypes by activating indiscriminate nucleases3,4,5. 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.

DOI: 10.1038/s41586-022-05559-3

Source: https://www.nature.com/articles/s41586-022-05559-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html